In
multicellular organisms
A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism.
All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni ...
, stem cells are
undifferentiated or partially differentiated
cells
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
that can differentiate into various
types of cells
There are many different types of cells in the human body.
Cells derived primarily from endoderm
Exocrine secretory epithelial cells
* Brunner's gland cell in duodenum (enzymes and alkaline mucus)
*Insulated goblet cell of respiratory and ...
and
proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a
cell lineage
Cell lineage denotes the developmental history of a tissue or organ from the fertilized embryo. This is based on the tracking of an organism's cellular ancestry due to the cell divisions and relocation as time progresses, this starts with the orig ...
.
They are found in both
embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
nic and adult organisms, but they have slightly different properties in each. They are usually distinguished from
progenitor cells
In genealogy, the progenitor (rarer: primogenitor; german: Stammvater or ''Ahnherr'') is the – sometimes legendary – founder of a family, line of descent, clan or tribe, noble house, or ethnic group..
Ebenda''Ahnherr:''"Stammvater eines G ...
, which cannot divide indefinitely, and
precursor
Precursor or Precursors may refer to:
* Precursor (religion), a forerunner, predecessor
** The Precursor, John the Baptist
Science and technology
* Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...
or blast cells, which are usually committed to differentiating into one cell type.
In
mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...
, roughly 50–150 cells make up the
inner cell mass
The inner cell mass (ICM) or embryoblast (known as the pluriblast in marsupials) is a structure in the early development of an embryo. It is the mass of cells inside the blastocyst that will eventually give rise to the definitive structures of th ...
during the
blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called th ...
stage of
embryonic development
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
, around days 5–14. These have stem-cell capability. ''
In vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...
'', they eventually differentiate into all of the body's cell types (making them
pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
). This process starts with the differentiation into the three
germ layers
A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three prim ...
– the
ectoderm
The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...
,
mesoderm
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Emb ...
and
endoderm
Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...
– at the
gastrulation
Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals the blastocyst is reorganized into a multilayered structure known as the gastrula. ...
stage. However, when they are isolated and
cultured ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'', they can be kept in the stem-cell stage and are known as
embryonic stem cells (ESCs).
Adult stem cells are found in a few select locations in the body, known as
niches, such as those in the
bone marrow
Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
or
gonads
A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...
. They exist to replenish rapidly lost cell types and are
multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
or unipotent, meaning they only differentiate into a few cell types or one type of cell. In mammals, they include, among others,
hematopoietic stem cells
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...
, which replenish blood and immune cells,
basal cells, which maintain the skin
epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
, and
mesenchymal stem cells
Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage c ...
, which maintain bone,
cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck ...
, muscle and fat cells. Adult stem cells are a small minority of cells; they are vastly outnumbered by the progenitor cells and terminally differentiated cells that they differentiate into.
Research into stem cells grew out of findings by Canadian biologists
Ernest McCulloch,
James Till and Andrew J. Becker at the
University of Toronto
The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
and the Ontario Cancer Institute in the 1960s. , the only established
medical therapy using stem cells is
hematopoietic stem cell transplantation
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
, first performed in 1958 by French oncologist
Georges Mathé. Since 1998 however, it has been possible to culture and differentiate human embryonic stem cells (in
stem-cell lines
A stem cell line is a group of stem cells that is cultured in vitro and can be propagated indefinitely. Stem cell lines are derived from either animal or human tissues and come from one of three sources: embryonic stem cells, adult stem cells, or ...
). The process of isolating these cells has been
controversial
Controversy is a state of prolonged public dispute or debate, usually concerning a matter of conflicting opinion or point of view. The word was coined from the Latin ''controversia'', as a composite of ''controversus'' – "turned in an opposite d ...
, because it typically results in the destruction of the embryo. Sources for isolating ESCs have been
restricted in some European countries and Canada, but others such as the UK and China have promoted the research.
Somatic cell nuclear transfer is a
cloning
Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, c ...
method that can be used to create a cloned embryo for the use of its embryonic stem cells in stem cell therapy. In 2006, a Japanese team led by
Shinya Yamanaka
is a Japanese stem cell researcher and a Nobel Prize laureate. He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyo ...
discovered a method to convert mature body cells back into stem cells. These were termed
induced pluripotent stem cells (iPSCs).
History
The term ''stem cell'' was coined by
Theodor Boveri
Theodor Heinrich Boveri (12 October 1862 – 15 October 1915) was a German zoologist, comparative anatomist and co-founder of modern cytology. He was notable for the first hypothesis regarding cellular processes that cause cancer, and for desc ...
and
Valentin Haecker in late 19th century.
Pioneering works in theory of blood stem cell were conducted in the beginning of 20th century by
Artur Pappenheim
Artur Pappenheim (13 December 1870 in Berlin – 31 December 1916) was a German physician and hematologist, remembered for his pioneer efforts in stem cell research.
Biography
Of Jewish origins, initially he studied mathematics and philosophy, ...
,
Alexander Maximow
Alexander Alexandrowitsch Maximow (russian: Александр Александрович Максимов; – December 4, 1928) was a Russian-American scientist in the fields of Histology and Embryology whose team developed the hypothesis about ...
,
Franz Ernst Christian Neumann
Franz Ernst Christian Neumann (30 January 1834 – 6 March 1918) was a German pathologist who was a native of Königsberg. His common name was Ernst Christian Neumann (without Franz at the beginning).
Life
He was the son of physicist Franz Ernst ...
.
The key properties of a stem cell were first defined by
Ernest McCulloch and
James Till at the University of Toronto and the Ontario Cancer Institute in the early 1960s. They discovered the blood-forming stem cell, the hematopoietic stem cell (HSC), through their pioneering work in mice. McCulloch and Till began a series of experiments in which bone marrow cells were injected into irradiated mice. They observed lumps in the spleens of the mice that were linearly proportional to the number of bone marrow cells injected. They hypothesized that each lump (colony) was a clone arising from a single marrow cell (stem cell). In subsequent work, McCulloch and Till, joined by graduate student
Andrew John Becker and senior scientist
Louis Siminovitch
Louis Siminovitch (May 1, 1920 – April 6, 2021) was a Canadian molecular biologist. He was a pioneer in human genetics, researcher into the genetic basis of muscular dystrophy and cystic fibrosis, and helped establish Ontario programs explori ...
, confirmed that each lump did in fact arise from a single cell. Their results were published in ''Nature'' in 1963. In that same year, Siminovitch was a lead investigator for studies that found colony-forming cells were capable of self-renewal, which is a key defining property of stem cells that Till and McCulloch had theorized.
The first therapy using stem cells was a
bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
performed by French oncologist
Georges Mathé in 1958 on five workers at the
Vinča Nuclear Institute in
Yugoslavia
Yugoslavia (; sh-Latn-Cyrl, separator=" / ", Jugoslavija, Југославија ; sl, Jugoslavija ; mk, Југославија ;; rup, Iugoslavia; hu, Jugoszlávia; rue, label= Pannonian Rusyn, Югославия, translit=Juhoslavij ...
who had been affected by a
criticality accident. The workers all survived.
In 1981, embryonic stem (ES) cells were first isolated and successfully cultured using mouse blastocysts by British biologists
Martin Evans and
Matthew Kaufman
Matthew H. Kaufman (29 September 1942 – 11 August 2013) was a British biologist. He was Professor Emeritus at University of Edinburgh having been Professor of Anatomy there from 1985 to 2007. He taught anatomy and embryology for more than 30 ...
. This allowed the formation of murine genetic models, a system in which the genes of mice are deleted or altered in order to study their function in pathology. By 1998, embryonic stem cells were first isolated by American biologist
James Thomson, which made it possible to have new transplantation methods or various cell types for testing new treatments. In 2006,
Shinya Yamanaka
is a Japanese stem cell researcher and a Nobel Prize laureate. He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyo ...
’s team in Kyoto, Japan converted fibroblasts into pluripotent stem cells by modifying the expression of only four genes. The feat represents the origin of induced pluripotent stem cells, known as iPS cells.
In 2011, a female
maned wolf
The maned wolf (''Chrysocyon brachyurus'') is a large canine of South America. It is found in Argentina, Brazil, Bolivia, Peru, and Paraguay, and is almost extinct in Uruguay. Its markings resemble those of foxes, but it is neither a fox nor a w ...
, run over by a truck, underwent stem cell treatment at the
Zoo Brasília, this being the first recorded case of the use of stem cells to heal injuries in a wild animal.
Properties
The classical definition of a stem cell requires that it possesses two properties:
* Self-renewal: the ability to go through numerous
cycles of
cell growth
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater th ...
and
cell division
Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ...
, known as
cell proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation r ...
, while maintaining the undifferentiated state.
*
Potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
: the capacity to
differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either
totipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
or
pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
—to be able to give rise to any mature cell type, although
multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
or
unipotent
In mathematics, a unipotent element ''r'' of a ring ''R'' is one such that ''r'' − 1 is a nilpotent element; in other words, (''r'' − 1)''n'' is zero for some ''n''.
In particular, a square matrix ''M'' is a unipotent ...
progenitor cell
A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...
s are sometimes referred to as stem cells. Apart from this, it is said that stem cell function is regulated in a feedback mechanism.
Self-renewal
Two mechanisms ensure that a stem cell population is maintained (doesn't shrink in size):
1.
Asymmetric cell division
An asymmetric cell division produces two daughter cells with different cellular fates. This is in contrast to symmetric cell divisions which give rise to daughter cells of equivalent fates. Notably, stem cells divide asymmetrically to give rise t ...
: a stem cell divides into one mother cell, which is identical to the original stem cell, and another daughter cell, which is differentiated.
When a stem cell self-renews, it divides and does not disrupt the undifferentiated state. This self-renewal demands control of cell cycle as well as upkeep of multipotency or pluripotency, which all depends on the stem cell.
2. Stochastic differentiation: when one stem cell grows and divides into two differentiated daughter cells, another stem cell undergoes
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
and produces two stem cells identical to the original.
Stem cells use
telomerase
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most euka ...
, a protein that restores
telomeres
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
, to protect their DNA and extend their cell division limit (the
Hayflick limit).
Potency meaning
Potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.
*
Totipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
(also known as omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism.
[ These cells are produced from the ]fusion
Fusion, or synthesis, is the process of combining two or more distinct entities into a new whole.
Fusion may also refer to:
Science and technology Physics
*Nuclear fusion, multiple atomic nuclei combining to form one or more different atomic nucl ...
of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.
* Pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,[ i.e. cells derived from any of the three ]germ layer
A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three pr ...
s.
* Multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
stem cells can differentiate into a number of cell types, but only those of a closely related family of cells.[
* Oligopotent stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells.][
* ]Unipotent
In mathematics, a unipotent element ''r'' of a ring ''R'' is one such that ''r'' − 1 is a nilpotent element; in other words, (''r'' − 1)''n'' is zero for some ''n''.
In particular, a square matrix ''M'' is a unipotent ...
cells can produce only one cell type, their own,[ but have the property of self-renewal, which distinguishes them from non-stem cells
]
Identification
In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cell
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within t ...
s (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'', using methods such as clonogenic assay A clonogenic assay is a cell biology technique for studying the effectiveness of specific agents on the survival and proliferation of cells. It is frequently used in cancer research laboratories to determine the effect of drugs or radiation on proli ...
s, in which single cells are assessed for their ability to differentiate and self-renew. Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, ''in vitro'' culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner ''in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
''. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.
Embryonic
Embryonic stem cell
Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consi ...
s (ESCs) are the cells of the inner cell mass
The inner cell mass (ICM) or embryoblast (known as the pluriblast in marsupials) is a structure in the early development of an embryo. It is the mass of cells inside the blastocyst that will eventually give rise to the definitive structures of th ...
of a blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called th ...
, formed prior to implantation in the uterus. In human embryonic development
Human embryonic development, or human embryogenesis, is the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of de ...
the blastocyst
The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called th ...
stage is reached 4–5 days after fertilization
Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
, at which time it consists of 50–150 cells. ESCs are pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
and give rise during development to all derivatives of the three germ layer
A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three pr ...
s: ectoderm
The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...
, endoderm
Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...
and mesoderm
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Emb ...
. In other words, they can develop into each of the more than 200 cell types of the adult body
Body may refer to:
In science
* Physical body, an object in physics that represents a large amount, has mass or takes up space
* Body (biology), the physical material of an organism
* Body plan, the physical features shared by a group of anima ...
when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extraembryonic membrane The extraembryonic membranes are four membranes which assist in the development of an animal's embryo. Such membranes occur in a range of animals from humans to insects. They originate from the embryo, but are not considered part of it. They typ ...
s or to the placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
.
During embryonic development the cells of the inner cell mass continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as 'neurectoderm
Neuroectoderm (or neural ectoderm or neural tube epithelium) consists of cells derived from ectoderm. Formation of the neuroectoderm is first step in the development of the nervous system. The neuroectoderm receives bone morphogenetic protein-in ...
', which will become the future central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
. Later in development, neurulation
Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube. The embryo at this stage is termed the neurula.
The process begins when the notochord induces the formati ...
causes the neurectoderm to form the neural tube
In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, a ...
. At the neural tube stage, the anterior portion undergoes encephalization
Encephalization quotient (EQ), encephalization level (EL), or just encephalization is a relative brain size measure that is defined as the ratio between observed to predicted brain mass for an animal of a given size, based on nonlinear regressi ...
to generate or 'pattern' the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell
Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor ste ...
.
The neural stem cells self-renew and at some point transition into radial glial progenitor cells (RGPs). Early-formed RGPs self-renew by symmetrical division to form a reservoir group of progenitor cell
A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...
s. These cells transition to a neurogenic
In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...
state and start to divide asymmetrically to produce a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from radial glial cells is called neurogenesis
Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs) ...
. The radial glial cell, has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall. It shares some glial
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
characteristics, most notably the expression of glial fibrillary acidic protein
Glial fibrillary acidic protein (GFAP) is a protein that is encoded by the ''GFAP'' gene in humans. It is a type III intermediate filament (IF) protein that is expressed by numerous cell types of the central nervous system (CNS), including astroc ...
(GFAP). The radial glial cell is the primary neural stem cell of the developing vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
CNS, and its cell body resides in the ventricular zone
In vertebrates, the ventricular zone (VZ) is a transient embryonic layer of tissue containing neural stem cells, principally radial glial cells, of the central nervous system (CNS). The VZ is so named because it lines the ventricular system, whic ...
, adjacent to the developing ventricular system
The ventricular system is a set of four interconnected cavities known as cerebral ventricles in the brain. Within each ventricle is a region of choroid plexus which produces the circulating cerebrospinal fluid (CSF). The ventricular system is con ...
. Neural stem cells are committed to the neuronal lineages (neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s, astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
s, and oligodendrocyte
Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...
s), and thus their potency is restricted.
Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin
Gelatin or gelatine (from la, gelatus meaning "stiff" or "frozen") is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also ...
as an extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
(for support) and require the presence of leukemia inhibitory factor
Leukemia inhibitory factor, or LIF, is an interleukin 6 class cytokine that affects cell growth by inhibiting differentiation. When LIF levels drop, the cells differentiate.
Function
LIF derives its name from its ability to induce the terminal ...
(LIF) in serum media. A drug cocktail containing inhibitors to GSK3B
Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the ''GSK3B'' gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased suscept ...
and the MAPK/ERK pathway
The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.
The signal starts when a signaling ...
, called 2i, has also been shown to maintain pluripotency in stem cell culture. Human ESCs are grown on a feeder layer of mouse embryonic fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...
and require the presence of basic fibroblast growth factor (bFGF or FGF-2). Without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4
Oct-4 (octamer-binding transcription factor 4), also known as POU5F1 ( POU domain, class 5, transcription factor 1), is a protein that in humans is encoded by the ''POU5F1'' gene. Oct-4 is a homeodomain transcription factor of the POU family. ...
, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency. The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 Stage-specific embryonic antigen 3 (SSEA-3) is a glycosphingolipid, specifically, an oligosaccharide composed of five carbohydrate units connected to a sphingolipid. Sphingolipids were originally discovered in 1884 by Johann Ludwig Wilhelm Thudichum ...
and 4, and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.
By using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They can then study these specialized adult cells in detail to try to discern complications of diseases, or to study cell reactions to proposed new drugs.
Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine
Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...
and tissue replacement after injury or disease., however, there are currently no approved treatments using ES cells. The first human trial was approved by the US Food and Drug Administration in January 2009. However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research
Spinal cord injury research seeks new ways to cure or treat spinal cord injury in order to lessen the debilitating effects of the injury in the short or long term. There is no cure for SCI, and current treatments are mostly focused on spinal cord ...
. On November 14, 2011 the company conducting the trial (Geron Corporation
Geron Corporation is a biotechnology company located in Foster City, California, Foster City, California, which specializes in developing and commercializing therapeutic products for cancer that inhibit telomerase.
Company information
Geron, ba ...
) announced that it will discontinue further development of its stem cell programs. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face. Embryonic stem cells, being pluripotent, require specific signals for correct differentiation – if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma
A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx.
Symptoms
Symptoms may be minimal if the tumor is small. A testicular terato ...
. Ethical considerations regarding the use of unborn human tissue are another reason for the lack of approved treatments using embryonic stem cells. Many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines.
File:Mouse embryonic stem cells.jpg, Mouse
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
embryonic
Embryonic may refer to:
*Of or relating to an embryo
* ''Embryonic'' (album), a 2009 studio album by the Flaming Lips
*''Embryonics
''Embryonics'' is a double-CD compilation of tracks by the Australian progressive metal band, Alchemist. It w ...
stem cells with fluorescent marker
File:Human embryonic stem cell colony phase.jpg, Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer
Mesenchymal stem cells
Mesenchymal stem cells (MSC) or mesenchymal stromal cells, also known as medicinal signaling cells are known to be multipotent, which can be found in adult tissues, for example, in the muscle, liver, bone marrow and adipose tissue. Mesenchymal stem cells usually function as structural support in various organs as mentioned above, and control the movement of substances. MSC can differentiate into numerous cell categories as an illustration of adipocytes, osteocytes, and chondrocytes, derived by the mesodermal layer. Where the mesoderm layer provides an increase to the body’s skeletal elements, such as relating to the cartilage or bone. The term “meso” means middle, infusion originated from the Greek, signifying that mesenchymal cells are able to range and travel in early embryonic growth among the ectodermal and endodermal layers. This mechanism helps with space-filling thus, key for repairing wounds in adult organisms that have to do with mesenchymal cells in the dermis (skin), bone, or muscle.
Mesenchymal stem cells are known to be essential for regenerative medicine. They are broadly studied in clinical trials
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
. Since they are easily isolated and obtain high yield, high plasticity, which makes able to facilitate inflammation and encourage cell growth, cell differentiation, and restoring tissue derived from immunomodulation and immunosuppression. MSC comes from the bone marrow, which requires an aggressive procedure when it comes to isolating the quantity and quality of the isolated cell, and it varies by how old the donor. When comparing the rates of MSC in the bone marrow aspirates and bone marrow stroma, the aspirates tend to have lower rates of MSC than the stroma. MSC are known to be heterogeneous, and they express a high level of pluripotent markers when compared to other types of stem cells, such as embryonic stem cells. MSCs injection leads to wound healing primarily through stimulation of angiogenesis.
Cell cycle control
Embryonic stem cells (ESCs) have the ability to divide indefinitely while keeping their pluripotency Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
, which is made possible through specialized mechanisms of cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
control. Compared to proliferating somatic cell
A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...
s, ESCs have unique cell cycle characteristics—such as rapid cell division caused by shortened G1 phase
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leadi ...
, absent G0 phase
The G0 phase describes a cellular state outside of the replicative cell cycle. Classically, cells were thought to enter G0 primarily due to environmental factors, like nutrient deprivation, that limited the resources necessary for proliferation ...
, and modifications in cell cycle checkpoint
Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, wi ...
s—which leaves the cells mostly in S phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...
at any given time. ESCs’ rapid division is demonstrated by their short doubling time, which ranges from 8 to 10 hours, whereas somatic cells have doubling time of approximately 20 hours or longer. As cells differentiate, these properties change: G1 and G2 phases lengthen, leading to longer cell division cycles. This suggests that a specific cell cycle structure may contribute to the establishment of pluripotency.
Particularly because G1 phase is the phase in which cells have increased sensitivity to differentiation, shortened G1 is one of the key characteristics of ESCs and plays an important role in maintaining undifferentiated phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
. Although the exact molecular mechanism remains only partially understood, several studies have shown insight on how ESCs progress through G1—and potentially other phases—so rapidly.
The cell cycle is regulated by complex network of cyclin
Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle.
Etymology
Cyclins were originally disco ...
s, cyclin-dependent kinase
Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They a ...
s (Cdk), cyclin-dependent kinase inhibitor
A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). Several function as tumor suppressor proteins. Cell cycle
The cell cycle, or cell-division cycle, is the series of events t ...
s (Cdkn), pocket proteins of the retinoblastoma (Rb) family, and other accessory factors. Foundational insight into the distinctive regulation of ESC cell cycle was gained by studies on mouse ESCs (mESCs). mESCs showed a cell cycle with highly abbreviated G1 phase, which enabled cells to rapidly alternate between M phase and S phase. In a somatic cell cycle, oscillatory activity of Cyclin-Cdk complexes is observed in sequential action, which controls crucial regulators of the cell cycle to induce unidirectional transitions between phases: Cyclin D
Cyclin D is a member of the cyclin protein family that is involved in regulating cell cycle progression. The synthesis of cyclin D is initiated during G1 and drives the G1/S phase transition. Cyclin D protein is anywhere from 155 (in zebra mu ...
and Cdk4/6 are active in the G1 phase, while Cyclin E
Cyclin E is a member of the cyclin family.
Cyclin E binds to G1 phase Cdk2, which is required for the transition from G1 to S phase of the cell cycle that determines initiation of DNA duplication. The Cyclin E/CDK2 complex phosphorylates p27 ...
and Cdk2
Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ''CDK2'' gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein ...
are active during the late G1 phase and S phase; and Cyclin A
Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. The stages that a cell passes through that culminate in its division and replication are collectively known as the cel ...
and Cdk2 are active in the S phase and G2, while Cyclin B
Cyclin B is a member of the cyclin family. Cyclin B is a mitotic cyclin. The amount of cyclin B (which binds to Cdk1) and the activity of the cyclin B-Cdk complex rise through the cell cycle until mitosis, where they fall abruptly due to degr ...
and Cdk1
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...
are active in G2 and M phase. However, in mESCs, this typically ordered and oscillatory activity of Cyclin-Cdk complexes is absent. Rather, the Cyclin E/Cdk2 complex is constitutively active throughout the cycle, keeping retinoblastoma protein
The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive ...
(pRb) hyperphosphorylated
Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problem ...
and thus inactive. This allows for direct transition from M phase to the late G1 phase, leading to absence of D-type cyclins and therefore a shortened G1 phase. Cdk2 activity is crucial for both cell cycle regulation and cell-fate decisions in mESCs; downregulation of Cdk2 activity prolongs G1 phase progression, establishes a somatic cell-like cell cycle, and induces expression of differentiation markers.
In human ESCs (hESCs), the duration of G1 is dramatically shortened. This has been attributed to high mRNA levels of G1-related Cyclin D2 and Cdk4 genes and low levels of cell cycle regulatory proteins that inhibit cell cycle progression at G1, such as p21CipP1, p27Kip1, and p57Kip2. Furthermore, regulators of Cdk4 and Cdk6 activity, such as members of the Ink family of inhibitors (p15, p16, p18, and p19), are expressed at low levels or not at all. Thus, similar to mESCs, hESCs show high Cdk activity, with Cdk2 exhibiting the highest kinase activity. Also similar to mESCs, hESCs demonstrate the importance of Cdk2 in G1 phase regulation by showing that G1 to S transition is delayed when Cdk2 activity is inhibited and G1 is arrest when Cdk2 is knocked down. However unlike mESCs, hESCs have a functional G1 phase. hESCs show that the activities of Cyclin E/Cdk2 and Cyclin A/Cdk2 complexes are cell cycle-dependent and the Rb checkpoint in G1 is functional.
ESCs are also characterized by G1 checkpoint non-functionality, even though the G1 checkpoint is crucial for maintaining genomic stability. In response to DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
, ESCs do not stop in G1 to repair DNA damages but instead, depend on S and G2/M checkpoints or undergo apoptosis. The absence of G1 checkpoint in ESCs allows for the removal of cells with damaged DNA, hence avoiding potential mutations from inaccurate DNA repair. Consistent with this idea, ESCs are hypersensitive to DNA damage to minimize mutations passed onto the next generation.
Fetal
The primitive stem cells located in the organs of fetuses
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...
are referred to as fetal stem cells.[
]
There are two types of fetal stem cells:
# Fetal proper stem cells come from the tissue of the fetus proper and are generally obtained after an abortion
Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregn ...
. These stem cells are not immortal but have a high level of division and are multipotent.
# Extraembryonic fetal stem cells come from extraembryonic membrane The extraembryonic membranes are four membranes which assist in the development of an animal's embryo. Such membranes occur in a range of animals from humans to insects. They originate from the embryo, but are not considered part of it. They typ ...
s, and are generally not distinguished from adult stem cells. These stem cells are acquired after birth, they are not immortal but have a high level of cell division, and are pluripotent.
Adult
Adult stem cells, also called somatic
Somatic may refer to:
* Somatic (biology), referring to the cells of the body in contrast to the germ line cells
** Somatic cell, a non-gametic cell in a multicellular organism
* Somatic nervous system, the portion of the vertebrate nervous sys ...
(from Greek σωματικóς, "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found. They can be found in children, as well as adults.
There are three known accessible sources of autologous
Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek).
The autologous tissue (also called autogenous, autogene ...
adult stem cells in humans:
# Bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
, which requires extraction by ''harvesting'', usually from pelvic bones via surgery.
# Adipose tissue (fat cells), which requires extraction by liposuction.
# Blood, which requires extraction through apheresis
Apheresis ( ἀφαίρεσις (''aphairesis'', "a taking away")) is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation ...
, wherein blood is drawn from the donor (similar to a blood donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor.
Stem cells can also be taken from umbilical cord blood
Cord blood (umbilical cord blood) is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders su ...
just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank their own blood for elective surgical procedures.
Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues. Bone marrow is a rich source of adult stem cells, which have been used in treating several conditions including liver cirrhosis, chronic limb ischemia and endstage heart failure. The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years. Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities. DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear ...
).
Most adult stem cells are lineage-restricted (multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
) and are generally referred to by their tissue origin (mesenchymal stem cell
Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage c ...
, adipose-derived stem cell, endothelial stem cell
Endothelial stem cells (ESCs) are one of three types of stem cells found in bone marrow. They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types. ESCs have t ...
, dental pulp stem cell Dental pulp stem cells (DPSCs) are stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the ...
, etc.). Muse cell A Muse cell (Multi-lineage differentiating stress enduring cell) is an endogenous non-cancerous pluripotent stem cell. They reside in the connective tissue of nearly every organ including the umbilical cord, bone marrow and peripheral blood. They a ...
s (multi-lineage differentiating stress enduring cells) are a recently discovered pluripotent stem cell type found in multiple adult tissues, including adipose, dermal fibroblasts, and bone marrow. While rare, muse cells are identifiable by their expression of SSEA-3 Stage-specific embryonic antigen 3 (SSEA-3) is a glycosphingolipid, specifically, an oligosaccharide composed of five carbohydrate units connected to a sphingolipid. Sphingolipids were originally discovered in 1884 by Johann Ludwig Wilhelm Thudichum ...
, a marker for undifferentiated stem cells, and general mesenchymal stem cells markers such as CD90, CD105
Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefor ...
. When subjected to single cell suspension culture, the cells will generate clusters that are similar to embryoid bodies in morphology as well as gene expression, including canonical pluripotency markers Oct4
Oct-4 (octamer-binding transcription factor 4), also known as POU5F1 (POU domain, class 5, transcription factor 1), is a protein that in humans is encoded by the ''POU5F1'' gene. Oct-4 is a homeodomain transcription factor of the POU family. I ...
, Sox2, and Nanog.
Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.
The use of adult stem cells in research and therapy is not as controversial
Controversy is a state of prolonged public dispute or debate, usually concerning a matter of conflicting opinion or point of view. The word was coined from the Latin ''controversia'', as a composite of ''controversus'' – "turned in an opposite d ...
as the use of embryonic stem cell
Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consi ...
s, because the production of adult stem cells does not require the destruction of an embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft
Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek).
The autologous tissue (also called autogenous, autogene ...
), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.
With the increasing demand of human adult stem cells for both research and clinical purposes (typically 1–5 million cells per kg of body weight are required per treatment) it becomes of utmost importance to bridge the gap between the need to expand the cells in vitro and the capability of harnessing the factors underlying replicative senescence. Adult stem cells are known to have a limited lifespan in vitro and to enter replicative senescence almost undetectably upon starting in vitro culturing.
Amniotic
Also called perinatal stem cells, these multipotent stem cells are found in amniotic fluid
The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...
and umbilical cord blood. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells Amniotic stem cells are the mixture of stem cells that can be obtained from the amniotic fluid as well as the amniotic membrane. They can develop into various tissue types including skin, cartilage, cardiac tissue, nerves, muscle, and bone. The cell ...
are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.
Amniotic stem cells are a topic of active research.
Use of stem cells from amniotic fluid
The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...
overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic
Roman or Romans most often refers to:
*Rome, the capital city of Italy
*Ancient Rome, Roman civilization from 8th century BC to 5th century AD
*Roman people, the people of ancient Rome
*'' Epistle to the Romans'', shortened to ''Romans'', a lette ...
teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican
Vatican may refer to:
Vatican City, the city-state ruled by the pope in Rome, including St. Peter's Basilica, Sistine Chapel, Vatican Museum
The Holy See
* The Holy See, the governing body of the Catholic Church and sovereign entity recognized ...
newspaper "Osservatore Romano
''L'Osservatore Romano'' (, 'The Roman Observer') is the daily newspaper of Vatican City State which reports on the activities of the Holy See and events taking place in the Catholic Church and the world. It is owned by the Holy See but is not a ...
" called amniotic stem cells "the future of medicine".
It is possible to collect amniotic stem cells for donors or for autologous use: the first US amniotic stem cells bank was opened in 2009 in Medford, MA, by Biocell Center Biocell Center is an international company specializing in the cryopreservation and private banking of amniotic fluid stem cells. The company is headquartered in Italy with several international locations and is involved with numerous partnerships ...
Corporation and collaborates with various hospitals and universities all over the world.
Induced pluripotent
Adult stem cells have limitations with their potency; unlike embryonic stem cell
Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consi ...
s (ESCs), they are not able to differentiate into cells from all three germ layers
A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three prim ...
. As such, they are deemed multipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
.
However, reprogramming
In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.
...
allows for the creation of pluripotent cells, induced pluripotent stem cell
Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in ...
s (iPSCs), from adult cells. These are not adult stem cells, but somatic cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. Using genetic reprogramming with protein transcription factors
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The func ...
, pluripotent stem cells with ESC-like capabilities have been derived. The first demonstration of induced pluripotent stem cells was conducted by Shinya Yamanaka
is a Japanese stem cell researcher and a Nobel Prize laureate. He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyo ...
and his colleagues at Kyoto University
, mottoeng = Freedom of academic culture
, established =
, type = National university, Public (National)
, endowment = ¥ 316 billion (2.4 1000000000 (number), billion USD)
, faculty = 3,480 (Teaching Staff)
, administrative_staff ...
. They used the transcription factors Oct3/4
Oct-4 (octamer-binding transcription factor 4), also known as POU5F1 (POU domain, class 5, transcription factor 1), is a protein that in humans is encoded by the ''POU5F1'' gene. Oct-4 is a homeodomain transcription factor of the POU family. I ...
, Sox2, c-Myc
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' (MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes referre ...
, and Klf4 to reprogram mouse fibroblast cells into pluripotent cells. Subsequent work used these factors to induce pluripotency in human fibroblast cells. Junying Yu
Junying Yu (born 1975) is a Chinese stem cell biologist. She is a researcher at the University of Wisconsin–Madison.
Biography
Yu was born in 1975 in Zhejiang, China. In 1997, Yu graduated from the Department of Biology of Peking University ...
, James Thomson, and their colleagues at the University of Wisconsin–Madison
A university () is an educational institution, institution of higher education, higher (or Tertiary education, tertiary) education and research which awards academic degrees in several Discipline (academia), academic disciplines. Universities ty ...
used a different set of factors, Oct4, Sox2, Nanog and Lin28, and carried out their experiments using cells from human foreskin
In male human anatomy, the foreskin, also known as the prepuce, is the double-layered fold of skin, mucosal and muscular tissue at the distal end of the human penis that covers the glans and the urinary meatus. The foreskin is attached to the g ...
. However, they were able to replicate Yamanaka Yamanaka (written: ; lit: "middle of mountain") is a Japanese surname. Notable people with the surname include:
* Akira Joe Yamanaka, singer for the Flower Travellin' Band
* Akiko Yamanaka (born 1945), Japanese politician of the Liberal Democratic ...
's finding that inducing pluripotency in human cells was possible.
Induced pluripotent stem cells differ from embryonic stem cells. They share many similar properties, such as pluripotency Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
and differentiation potential, the expression of pluripotency Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
genes, epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
patterns, embryoid body
Embryoid bodies (EBs) are three-dimensional aggregates of pluripotent stem cells.
EBs are differentiation of human embryonic stem cells into embryoid bodies comprising the three embryonic germ layers.
Background
The pluripotent cell type ...
and teratoma
A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx.
Symptoms
Symptoms may be minimal if the tumor is small. A testicular terato ...
formation, and viable chimera
Chimera, Chimaera, or Chimaira (Greek for " she-goat") originally referred to:
* Chimera (mythology), a fire-breathing monster of Ancient Lycia said to combine parts from multiple animals
* Mount Chimaera, a fire-spewing region of Lycia or Cilicia ...
formation, but there are many differences within these properties. The chromatin of iPSCs appears to be more "closed" or methylated than that of ESCs. Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins. There are thus questions about the "completeness" of reprogramming
In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.
...
and the somatic memory of induced pluripotent stem cells. Despite this, inducing somatic cells to be pluripotent appears to be viable.
As a result of the success of these experiments, Ian Wilmut
Sir Ian Wilmut, OBE FRS -- FMedSci FRSE (born 7 July 1944) is an English embryologist and Chair of the Scottish Centre for Regenerative Medicine at the University of Edinburgh. He is best known as the leader of the research group that in 19 ...
, who helped create the first cloned animal Dolly the Sheep
Dolly (5 July 1996 – 14 February 2003) was a female Finnish Dorset sheep and the first mammal cloned from an adult somatic cell. She was cloned by associates of the Roslin Institute in Scotland, using the process of nuclear transfer from a ...
, has announced that he will abandon somatic cell nuclear transfer
In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte (egg cell) and implanting a ...
as an avenue of research.
IPSCs has helped the field of medicine significantly by finding numerous ways to cure diseases. Since human IPSCc has given the advantage to make ''in vitro'' models to study toxins and pathogenesis.
Furthermore, induced pluripotent stem cells provide several therapeutic advantages. Like ESCs, they are pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
. They thus have great differentiation potential; theoretically, they could produce any cell within the human body (if reprogramming
In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.
...
to pluripotency was "complete"). Moreover, unlike ESCs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient. Frozen blood samples can be used as a valuable source of induced pluripotent stem cells. Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection. Despite their current limited use therapeutically, iPSCs hold great potential for future use in medical treatment and research.
Cell cycle control
The key factors controlling the cell cycle also regulate pluripotency Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta.
According to Latin terms, Pluripotentia means the ability for many thin ...
. Thus, manipulation of relevant genes can maintain pluripotency and reprogram somatic cells to an induced pluripotent state. However, reprogramming of somatic cells is often low in efficiency and considered stochastic
Stochastic (, ) refers to the property of being well described by a random probability distribution. Although stochasticity and randomness are distinct in that the former refers to a modeling approach and the latter refers to phenomena themselv ...
.
With the idea that a more rapid cell cycle is a key component of pluripotency, reprogramming efficiency can be improved. Methods for improving pluripotency through manipulation of cell cycle regulators include: overexpression of Cyclin D/Cdk4, phosphorylation of Sox2 at S39 and S253, overexpression of Cyclin A and Cyclin E, knockdown of Rb, and knockdown of members of the Cip/Kip family or the Ink family. Furthermore, reprogramming efficiency is correlated with the number of cell divisions happened during the stochastic phase, which is suggested by the growing inefficiency of reprogramming of older or slow diving cells.
Lineage
Lineage is an important procedure to analyze developing embryos. Since cell lineages shows the relationship between cells at each division. This helps in analyzing stem cell lineages along the way which helps recognize stem cell effectiveness, lifespan, and other factors. With the technique of cell lineage mutant genes can be analyzed in stem cell clones that can help in genetic pathways. These pathways can regulate how the stem cell perform.
To ensure self-renewal, stem cells undergo two types of cell division (see ''Stem cell division and differentiation'' diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell
A progenitor cell is a Cell (biology), biological cell that can Cellular differentiation, differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor ...
with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
) between the daughter cells.
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche
Niche may refer to:
Science
*Developmental niche, a concept for understanding the cultural context of child development
*Ecological niche, a term describing the relational position of an organism's species
*Niche differentiation, in ecology, the ...
. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in ''Drosophila'' germarium have identified the signals decapentaplegic
Decapentaplegic (Dpp) is a key morphogen involved in the development of the fruit fly ''Drosophila melanogaster'' and is the first validated secreted morphogen. It is known to be necessary for the correct patterning and development of the early '' ...
and adherens junctions that prevent germarium stem cells from differentiating.
Therapies
Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
is a form of stem cell therapy that has been used for many years because it has proven to be effective in clinical trials.[Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation]
In National Cancer Institute Fact Sheet web site. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2010. Cited August 24, 2010
Stem cell implantation may help in strengthening the left-ventricle of the heart, as well as retaining the heart tissue to patients who have suffered from heart attacks in the past.
Advantages
Stem cell treatments may lower symptoms of the disease or condition that is being treated. The lowering of symptoms may allow patients to reduce the drug intake of the disease or condition. Stem cell treatment may also provide knowledge for society to further stem cell understanding and future treatments. The physicians' creed would be to do no injury, and stem cells make that simpler than ever before. Surgical processes by their character are harmful. Tissue has to be dropped as a way to reach a successful outcome. One may prevent the dangers of surgical interventions using stem cells. Additionally, there's a possibility of disease, and whether the procedure fails, further surgery may be required. Risks associated with anesthesia can also be eliminated with stem cells. On top of that, stem cells have been harvested from the patient's body and redeployed in which they're wanted. Since they come from the patient’s own body, this is referred to as an autologous treatment. Autologous remedies are thought to be the safest because there's likely zero probability of donor substance rejection.
Disadvantages
Stem cell treatments may require immunosuppression
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.
Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types.
Some stem cells form tumors after transplantation;[Bernadine Healy, M.D.]
"Why Embryonic Stem Cells are obsolete"
''US News and world report''. Retrieved on Aug 17, 2015. pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.
Ethical concerns are also raised about the practice of using or researching embryonic stem cells. Harvesting cells from the blastocyst result in the death of the blastocyst. The concern is whether or not the blastocyst should be considered as a human life. The debate on this issue is mainly a philosophical one, not a scientific one.
Stem cell tourism
Stem cell tourism is the industry in which patients (and sometimes their families) travel to another jurisdiction, to obtain stem cell procedures which are not approved but which are advertised on the Internet as proven cures.
The United States, in recent years, has had an explosion of "stem cell clinics". Stem cell procedures are highly profitable for clinics. The advertising sounds authoritative but the efficacy and safety of the procedures is unproven. Patients sometimes experience complications, such as spinal tumors and death. The high expense can also lead to financial ruin. According to researchers, there is a need to educate the public, patients, and doctors about this issue.
According to the International Society for Stem Cell Research
The International Society for Stem Cell Research (ISSCR) is an independent 501(c)(3) nonprofit organization based in Skokie, Illinois, United States. The organization's mission is to promote excellence in stem cell science and applications to hum ...
, the largest academic organization that advocates for stem cell research, stem cell therapies are under development and cannot yet be said to be proven. Doctors should inform patients that clinical trials continue to investigate whether these therapies are safe and effective but that unethical clinics present them as proven.
Research
Some of the fundamental patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...
s covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation
The Wisconsin Alumni Research Foundation is the independent nonprofit technology transfer organization serving the University of Wisconsin–Madison and Morgridge Institute for Research. It provides significant research support, granting tens ...
(WARF) – they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson. WARF does not enforce these patents against academic scientists, but does enforce them against companies.[Regalado, Antonio, David P. Hamilton (July 2006)]
"How a University's Patents May Limit Stem-Cell Researcher."
''The Wall Street Journal''. Retrieved on July 24, 2006.
In 2006, a request for the US Patent and Trademark Office
The United States Patent and Trademark Office (USPTO) is an List of federal agencies in the United States, agency in the United States Department of Commerce, U.S. Department of Commerce that serves as the national patent office and trademark ...
(USPTO) to re-examine the three patents was filed by the Public Patent Foundation
In public relations and communication science, publics are groups of individual people, and the public (a.k.a. the general public) is the totality of such groupings. This is a different concept to the sociological concept of the ''Öffentlichkei ...
on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog
Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights) is a non-profit, progressive organization which advocates for taxpayer and consumer interests, with a focus on insurance, health care, political reform, privacy and ener ...
(formerly the Foundation for Taxpayer and Consumer Rights). In the re-examination process, which involves several rounds of discussion between the USPTO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents, however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not. Consumer Watchdog appealed the granting of the '913 patent to the USPTO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable. However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed.
In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US Court of Appeals for the Federal Circuit
The United States Court of Appeals for the Federal Circuit (in case citations, Fed. Cir. or C.A.F.C.) is a United States court of appeals that has special appellate jurisdiction over certain types of specialized cases in the U.S. federal court ...
(CAFC), the federal appeals court that hears patent cases. At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing
Law is a set of rules that are created and are law enforcement, enforceable by social or governmental institutions to regulate behavior,Robertson, ''Crimes against humanity'', 90. with its precise definition a matter of longstanding debate. ...
to appeal; the case could not proceed until that issue was resolved.
Investigations
Diseases and conditions where stem cell treatment is being investigated include:
* Diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
* Androgenic Alopecia and hair loss
* Rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
* Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
* Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
* Osteoarthritis
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...
[Stem Cell Basics: What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?](_blank)
In Stem Cell Information World Wide Web site. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009. cited Sunday, April 26, 2009
* Stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
and traumatic brain injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
repair
* Learning disability
Learning disability, learning disorder, or learning difficulty (British English) is a condition in the brain that causes difficulties comprehending or processing information and can be caused by several different factors. Given the "difficult ...
due to congenital disorder
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
* Spinal cord injury
A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cor ...
repair
* Heart infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when Hemodynamics, blood flow decreases or stops to the coronary artery of the heart, causing ischemia, damage to the cardiac muscle, heart muscle. The most common symptom i ...
* Anti-cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
treatments[
* ]Baldness
Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarrin ...
reversal
* Replace missing teeth
A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...
* Repair hearing
Hearing, or auditory perception, is the ability to perceive sounds
In physics, sound is a vibration that propagates as an acoustic wave, through a transmission medium such as a gas, liquid or solid.
In human physiology and psycholog ...
* Restore vision
Vision, Visions, or The Vision may refer to:
Perception Optical perception
* Visual perception, the sense of sight
* Visual system, the physical mechanism of eyesight
* Computer vision, a field dealing with how computers can be made to gain un ...
and repair damage to the cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...
* Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
* Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
* Wound healing
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
* Male infertility
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen, ...
due to absence of spermatogonial stem cells. In recent studies, scientist have found a way to solve this problem by reprogramming a cell and turning it into a spermatozoon. Other studies have proven the restoration of spermatogenesis by introducing human iPSC cells in mice testicles. This could mean the end of azoospermia
Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with male infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be seen ...
.
* Female infertility
Female infertility refers to infertility in women. It affects an estimated 48 million women, with the highest prevalence of infertility affecting women in South Asia, Sub-Saharan Africa, North Africa/Middle East, and Central/Eastern Europe and Cen ...
: oocytes made from embryonic stem cells. Scientists have found the ovarian stem cells, a rare type of cells (0.014%) found in the ovary. They could be used as a treatment not only for infertility, but also for premature ovarian insufficiency.
* Critical Limb Ischemia
Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
and conditions, diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, heart disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
, and other conditions. Research is also underway in generating organoid
An organoid is a miniaturized and simplified version of an Organ (anatomy), organ produced in vitro in three dimensions that shows realistic micro-anatomy. They are derived from one or a few Cell (biology), cells from a Tissue (biology), tissue, ...
s using stem cells, which would allow for further understanding of human development, organogenesis
Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal orga ...
, and modeling of human diseases.
In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists' growing ability to create stem cells using somatic cell nuclear transfer
In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte (egg cell) and implanting a ...
and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning
Human cloning is the creation of a genetically identical copy (or clone) of a human. The term is generally used to refer to artificial human cloning, which is the reproduction of human cells and tissue. It does not refer to the natural concepti ...
.
Hepatotoxicity
Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...
and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for re ...
process.
Notable studies
In August 2021, researchers in the Princess Margaret Cancer Centre
The Princess Margaret Cancer Centre (previously, ''Princess Margaret Hospital'') is a scientific research centre and a teaching hospital in Toronto, Ontario, Canada, affiliated with the University of Toronto Faculty of Medicine as part of the Univ ...
at the University Health Network
University Health Network (UHN) is a public research and teaching hospital network in Toronto, Ontario, Canada. It is the largest health research organization in Canada and ranks first in Canada for total research funding. It was named Canada's ...
published their discovery of a dormancy mechanism in key stem cells which could help develop cancer treatments in the future.
See also
* Cell bank A cell bank is a facility that stores cells of specific genome for the purpose of future use in a product or medicinal needs. They often contain expansive amounts of base cell material that can be utilized for various projects. Cell banks can be us ...
* Human genome
The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...
* Meristem
The meristem is a type of tissue found in plants. It consists of undifferentiated cells (meristematic cells) capable of cell division. Cells in the meristem can develop into all the other tissues and organs that occur in plants. These cells conti ...
* Mesenchymal stem cell
Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage c ...
* Ovarian stem cell
Ovarian stem cells are oocytes formed in ovarian follicle before birth in female mammals. They do not form post-natally, and are depleted throughout reproductive life. In humans it is estimated that 500,000–1,000,000 primordial follicles are pre ...
* Partial cloning
In the field of cell biology, the method of partial cloning (PCL) converts a fully differentiated ''old'' somatic cell into a partially reprogrammed ''young'' cell that retains all the specialised functions of the differentiated ''old'' cell but ...
* Plant stem cell
Plant stem cells
Plant stem cells are innately undifferentiated cells located in the meristems of plants. Plant stem cells serve as the origin of plant vitality, as they maintain themselves while providing a steady supply of precursor cells to ...
* Stem cell controversy
The stem cell controversy is the consideration of the ethics of research involving the development and use of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves human embryos. For e ...
* Stem cell marker Stem cell markers are genes and their protein products used by scientists to isolate and identify stem cells. Stem cells can also be identified by functional assays. Below is a list of genes/protein products that can be used to identify various typ ...
References
Further reading
*
External links
National Institutes of Health: Stem Cell Information
Nature.com: Stem Cells
{{DEFAULTSORT:Stem Cell
Induced stem cells
Biotechnology
Cell biology
Cloning
Developmental biology