Adult Stem Cell Research
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Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by
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 ar ...
to replenish dying cells and regenerate damaged tissues. Also known as somatic
stem cells 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 same stem cell. They are the earliest type of ...
(from Greek σωματικóς, meaning ''of the body''), they can be found in juvenile, adult animals, and humans, unlike
embryonic stem cells 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 consist ...
. Scientific interest in adult stem cells is centered around two main characteristics. The first of which, being their ability to divide or self-renew indefinitely, and secondly, their ability to generate all the
cell type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cell ...
s of the organ from which they originate, potentially regenerating the entire organ from a few cells. Unlike embryonic stem cells, the use of human adult stem cells in research and therapy is not considered to be
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 they are derived from adult tissue samples rather than human embryos designated for scientific research. The main functions of adult stem cells are to replace cells that are at risk of possibly dying as a result of disease or injury and to maintain a state of
homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
within the cell. There are three main methods to determine if the adult stem cell is capable of becoming a specialized cell. The adult stem cell can be labeled ''
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 ...
'' and tracked, it can be isolated and then transplanted back into the organism, and it can be isolated ''in vivo'' and manipulated with growth hormones. They have mainly been studied in humans and model organisms such as mice and
rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...
.


Structure


Defining properties

A stem cell possesses two properties: * ''Self-renewal'' is the ability to go through numerous cycles of
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 ar ...
while still maintaining its undifferentiated state. Stem cells are able to replicate several times and can result in the formation of two stem cells, one stem cell more differentiated than the other, or two differentiated cells. * ''
Multipotency 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 ''multidifferentiative potential'' is the ability to generate progeny of several distinct
cell type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cell ...
s, (for example
glial cell 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 myel ...
s and
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. ...
s) as opposed to
unipotency 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 the term for cells that are restricted to producing a single cell type. However, some researchers do not consider multipotency to be essential, and believe that
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 unipoten ...
self-renewing stem cells can exist. These properties can be illustrated with relative ease ''
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 ...
'', 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, where the progeny of a single cell is characterized. However, it is known that ''in vitro'' cell culture conditions can alter the behavior of cells, proving that a particular
subpopulation In statistics, a population is a Set (mathematics), set of similar items or events which is of interest for some question or experiment. A statistical population can be a group of existing objects (e.g. the set of all stars within the Milky Way g ...
of cells possesses stem cell properties ''in vivo'' is challenging, and so considerable debate exists as to whether some proposed stem cell populations in the adult are indeed stem cells.


Properties


Cell division

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 stem cells, whereas asymmetric division produces one stem cell and one
progenitor cell A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only differ ...
with limited self-renewal potential. Progenitors can go through several rounds of cell division before finally differentiating into a mature cell. It is believed 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 ...
) and their associated proteins between the daughter cells. Under normal conditions, tissue stem cells divide slowly and infrequently. They exhibit signs of quiescence, or reversible growth arrest. The
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 ...
the stem cell is found in plays a large role in maintaining quiescence. Perturbed niches cause the stem cell to begin actively dividing again to replace lost or damaged cells until the niche is restored. In hematopoietic stem cells, the MAPK/ERK pathway and PI3K/AKT/mTOR pathway regulate this transition. The ability to regulate the cell cycle in response to external cues helps prevent stem cell exhaustion, or the gradual loss of stem cells following an altered balance between dormant and active states. Infrequent cell divisions also help reduce the risk of acquiring DNA mutations that would be passed on to daughter cells.


Plasticity

Discoveries in recent years have suggested that adult stem cells might have the ability to differentiate into cell types from different germ layers. For instance, neural stem cells from the brain, which are derived from ectoderm, can differentiate into ectoderm, mesoderm, and endoderm. Stem cells from the bone marrow, which is derived from mesoderm, can differentiate into liver, lung, GI tract and skin, which are derived from endoderm and mesoderm. This phenomenon is referred to as stem cell
transdifferentiation Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type ...
or plasticity. It can be induced by modifying the growth medium when stem cells are cultured ''in vitro'' or transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity. More recent findings suggest that pluripotent stem cells may reside in blood and adult tissues in a dormant state. These cells are referred to as "Blastomere Like Stem Cells" (BLSCs) and "very small embryonic like" (VSEL) stem cells, and display pluripotency ''in vitro''. As BLSCs and VSEL cells are present in virtually all adult tissues, including lung, brain, kidneys, muscles, and pancreas, co-purification of BLSCs and VSEL cells with other populations of adult stem cells may explain the apparent pluripotency of adult stem cell populations. However, recent studies have shown that both human and murine VSEL cells lack stem cell characteristics and are not pluripotent.


Aging

Stem cell function becomes impaired with age, and this contributes to progressive deterioration of tissue maintenance and repair. A likely important cause of increasing stem cell dysfunction is age-dependent accumulation of DNA damage in both stem cells and the cells that comprise the stem cell environment. (See also
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 D ...
.) Adult stem cells can, however, be artificially reverted to a state where they behave like embryonic stem cells (including the associated DNA repair mechanisms). This was done with mice as early as 2006 with future prospects to slow down human aging substantially. Such cells are one of the various classes of
induced stem cells Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotent – ...
.


Function


Signaling pathways

Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation. * Notch :The
Notch pathway The Notch signaling pathway is a highly conserved cell signaling system present in most animals. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembr ...
has been known to developmental biologists for decades. Its role in control of stem cell proliferation has now been demonstrated for several cell types including
haematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
, neural, and
mammary A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in prima ...
stem cells. * Wnt :These developmental pathways are also strongly implicated as stem cell regulators. *
TGFβ Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sig ...
:The TGFβ family of
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s regulate the stemness of both normal and cancer stem cells.


Types


Hematopoietic stem cells

Hematopoietic stem cells (HSCs) are stem cells that can differentiate into all blood cells. This process is called haematopoiesis. Hematopoietic stem cells are found in the bone marrow and umbilical cord blood. The HSC are generally dormant when found in adults due to their nature.


Mammary stem cells

Mammary stem cells provide the source of cells for growth of the
mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in pri ...
during puberty and gestation and play an important role in
carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...
of the breast. Mammary stem cells have been isolated from human and mouse tissue as well as from
cell lines An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
derived from the mammary gland. Single such cells can give rise to both the luminal and
myoepithelial cell Myoepithelial cells (sometimes referred to as myoepithelium) are cells usually found in glandular epithelium as a thin layer above the basement membrane but generally beneath the luminal cells. These may be positive for alpha smooth muscle actin a ...
types of the gland and have been shown to have the ability to regenerate the entire organ in mice.


Intestinal stem cells

Intestinal stem cells divide continuously throughout life and use a complex genetic program to produce the cells lining the surface of the small and large intestines. Intestinal stem cells reside near the base of the stem cell niche, called the
crypts of Lieberkuhn A crypt (from Latin ''crypta'' "vault") is a stone chamber beneath the floor of a church or other building. It typically contains coffins, sarcophagi, or religious relics. Originally, crypts were typically found below the main apse of a chur ...
. Intestinal stem cells are probably the source of most cancers of the small intestine and colon.


Mesenchymal stem cells

Mesenchymal stem cells (MSCs) are of stromal origin and may differentiate into a variety of tissues. MSCs have been isolated from
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 mate ...
,
adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...
, lung, bone marrow and blood,
Wharton's jelly Wharton's jelly (''substantia gelatinea funiculi umbilicalis'') is a gelatinous substance within the umbilical cord, largely made up of mucopolysaccharides (hyaluronic acid and chondroitin sulfate). It acts as a mucous connective tissue containing ...
from the
umbilical cord In placental mammals, the umbilical cord (also called the navel string, birth cord or ''funiculus umbilicalis'') is a conduit between the developing embryo or fetus and the placenta. During prenatal development, the umbilical cord is physiologi ...
, and teeth (perivascular niche of
dental pulp The pulp is the connective tissue, nerves, blood vessels, and odontoblasts that comprise the innermost layer of a tooth. The pulp's activity and signalling processes regulate its behaviour. Anatomy The pulp is the neurovascular bundle centr ...
and
periodontal ligament The periodontal ligament, commonly abbreviated as the PDL, is a group of specialized connective tissue fibers that essentially attach a tooth to the alveolar bone within which it sits. It inserts into root cementum one side and onto alveolar b ...
). MSCs are attractive for clinical therapy due to their ability to differentiate, provide
trophic Trophic, from Ancient Greek τροφικός (''trophikos'') "pertaining to food or nourishment", may refer to: * Trophic cascade * Trophic coherence * Trophic egg * Trophic function * Trophic hormone * Trophic level index * Trophic level ...
support, and modulate innate immune response. These cells have the ability to differentiate into various cell types such as osteoblasts,
chondroblast Chondroblasts, or perichondrial cells, is the name given to mesenchymal progenitor cells in situ which, from endochondral ossification, will form chondrocytes in the growing cartilage matrix. Another name for them is subchondral cortico-spon ...
s, adipocytes,
neuroectoderm 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-inhi ...
al cells, and
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s. Bioactive mediators that favor local cell growth are also secreted by MSCs. Anti-inflammatory effects on the local microenvironment, which promote tissue healing, are also observed. The inflammatory response can be modulated by adipose-derived regenerative cells (ADRC) including mesenchymal stem cells and regulatory
T-lymphocytes A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
. The mesenchymal stem cells thus alter the outcome of the immune response by changing the cytokine secretion of dendritic and T-cell subsets. This results in a shift from a pro-inflammatory environment to an anti-inflammatory or tolerant cell environment.


Endothelial stem cells

Endothelial stem cells are one of the three types of multipotent stem cells found in the bone marrow. They are a rare and controversial group with the ability to differentiate into endothelial cells, the cells that line blood vessels as well as
lymphatic vessels The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessel ...
. Endothelial stem cells are an important aspect in the vascular network, even influencing the motion relating to white blood cells.


Neural stem cells

The existence of stem cells in the adult brain has been postulated following the discovery that the process of neurogenesis, the birth of new
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. ...
s, continues into adulthood in rats. The presence of stem cells in the mature primate brain was first reported in 1967. It has since been shown that new neurons are generated in adult mice, songbirds and primates, including humans. Normally, adult neurogenesis is restricted to two areas of the brain – the
subventricular zone The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zone ...
, which lines the
lateral ventricles The lateral ventricles are the two largest ventricles of the brain and contain cerebrospinal fluid (CSF). Each cerebral hemisphere contains a lateral ventricle, known as the left or right ventricle, respectively. Each lateral ventricle resemble ...
, and the
dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute t ...
of the
hippocampal formation The hippocampal formation is a compound structure in the Temporal lobe#Medial temporal lobe, medial temporal lobe of the brain. It forms a c-shaped bulge on the floor of the temporal horn of the Lateral ventricles, lateral ventricle. There is no ...
. Although the generation of new neurons in the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
is well established, the presence of true self-renewing stem cells there has been debated. Under certain circumstances, such as following tissue damage in
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
, neurogenesis can be induced in other brain regions, including the
neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
. Neural stem cells are commonly cultured ''in vitro'' as so called
neurospheres A neurosphere is a culture system composed of free-floating clusters of neural stem cells. Neurospheres provide a method to investigate neural precursor cells ''in vitro''. Putative neural stem cells are suspended in a medium lacking adherent s ...
– floating
heterogeneous Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, siz ...
aggregates of cells, containing a large proportion of stem cells. They can be propagated for extended periods of time and differentiated into both
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. ...
al and
glia 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 ...
cells, and therefore behave as stem cells. However, some recent studies suggest that this behaviour is induced by the culture conditions in
progenitor cell A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only differ ...
s, the progeny of stem cell division that normally undergo a strictly limited number of replication cycles ''in vivo''. Furthermore, neurosphere-derived cells do not behave as stem cells when transplanted back into the brain. Neural stem cells share many properties with
haematopoietic 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). Remarkably, when injected into the blood, neurosphere-derived cells differentiate into various cell types of the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
.


Olfactory adult stem cells

Olfactory adult stem cells have been successfully harvested from the human
olfactory mucosa The olfactory mucosa is located in the upper region of the nasal cavity and is made up of the olfactory epithelium and the underlying lamina propria, connective tissue containing fibroblasts, blood vessels, Bowman's glands and bundles of fine ax ...
cells, which are found in the lining of the nose and are involved in the sense of smell. If they are given the right chemical environment, these cells have the same ability as embryonic stem cells to develop into many different cell types. Olfactory stem cells hold the potential for therapeutic applications and, in contrast to neural stem cells, can be harvested with ease without harm to the patient. This means they can be easily obtained from all individuals, including older patients who might be most in need of stem cell therapies.


Neural crest stem cells

Hair follicle The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between h ...
s contain two types of stem cells, one of which appears to represent a remnant of the stem cells of the embryonic
neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...
. Similar cells have been found in the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
,
sciatic nerve The sciatic nerve, also called the ischiadic nerve, is a large nerve in humans and other vertebrate animals which is the largest branch of the sacral plexus and runs alongside the hip joint and down the lower limb. It is the longest and widest si ...
, cardiac outflow tract and spinal and
sympathetic ganglia The sympathetic ganglia, or paravertebral ganglia are autonomic ganglia, of the sympathetic nervous system. Ganglia are 20,000 to 30,000 afferent and efferent nerve cell bodies that run along on either side of the spinal cord. Afferent nerve c ...
. These cells can generate
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. ...
s,
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensh ...
s,
myofibroblast A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell. Structure Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-sm ...
,
chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...
s and
melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...
s.


Testicular cells

Multipotent stem cells with a claimed equivalency to embryonic stem cells have been derived from spermatogonial progenitor cells found in the
testicles A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...
of laboratory mice by scientists in Germany and the United States, and, a year later, researchers from Germany and the United Kingdom confirmed the same capability using cells from the testicles of humans. The extracted stem cells are known as human adult germline stem cells (GSCs) Multipotent stem cells have also been derived from
germ cell Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embry ...
s found in human testicles.


Clinical significance

Adult stem cell treatments have been used for many years to successfully treat
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
and related bone/blood cancers utilizing bone marrow transplants. The use of adult stem cells in research and therapy is not considered 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 cells 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 consist ...
, 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 ...
. Early regenerative applications of adult stem cells has focused on intravenous delivery of blood progenitors known as Hematopetic Stem Cells (HSC's). CD34+
hematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
Stem Cells have been clinically applied to treat various diseases including spinal cord injury, liver cirrhosis and Peripheral Vascular disease. Research has shown that CD34+
hematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
Stem Cells are relatively more numerous in men than in women of reproductive age group among spinal cord Injury victims. Other early commercial applications have focused on Mesenchymal Stem Cells (MSCs). For both cell lines, direct injection or placement of cells into a site in need of repair may be the preferred method of treatment, as vascular delivery suffers from a "pulmonary first pass effect" where intravenous injected cells are sequestered in the lungs. Clinical case reports in orthopedic applications have been published. Wakitani has published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects. Centeno et al. have reported high field MRI evidence of increased cartilage and meniscus volume in individual human clinical subjects as well as a large n=227 safety study. Many other stem cell based treatments are operating outside the US, with much controversy being reported regarding these treatments as some feel more regulation is needed as clinics tend to exaggerate claims of success and minimize or omit risks.


Therapies

The therapeutic potential of adult stem cells is the focus of much scientific research, due to their ability to be harvested from the parent body that is females during the delivery. In common with embryonic stem cells, adult stem cells have the ability to differentiate into more than one cell type, but unlike the former they are often restricted to certain types or "lineages". The ability of a differentiated stem cell of one lineage to produce cells of a different lineage is called
transdifferentiation Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type ...
. Some types of adult stem cells are more capable of transdifferentiation than others, but for many there is no evidence that such a transformation is possible. Consequently, adult stem therapies require a stem cell source of the specific lineage needed, and harvesting and/or culturing them up to the numbers required is a challenge. Additionally, cues from the immediate environment (including how stiff or porous the surrounding structure/
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 ...
is) can alter or enhance the fate and differentiation of the stem cells.


Sources

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, i.e. cells that can give rise to any fetal or adult cell type, can be found in a number of tissues, including umbilical cord blood. Using genetic reprogramming, pluripotent stem cells equivalent to
embryonic stem cells 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 consist ...
have been derived from human adult skin tissue. Other adult stem cells 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 ...
, meaning there are several limited types of cell they can become, and are generally referred to by their tissue origin (such as
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 ...
, etc.). A great deal of adult stem cell research has focused on investigating their capacity to divide or self-renew indefinitely, and their potential for differentiation. In mice, pluripotent stem cells can be directly generated from adult
fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
cultures.


Research


Cancer

In recent years, acceptance of the concept of adult stem cells has increased. There is now a hypothesis that stem cells reside in many adult tissues and that these unique reservoirs of cells not only are responsible for the normal reparative and regenerative processes but are also considered to be a prime target for genetic and
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 ...
changes, culminating in many abnormal conditions including cancer. (See cancer stem cell for more details.)


Multidrug resistance

Adult stem cells express transporters of the
ATP-binding cassette family The ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC trans ...
that actively pump a diversity of organic molecules out of the cell. Many pharmaceuticals are exported by these transporters conferring
multidrug resistance Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...
onto the cell. This complicates the design of drugs, for instance
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 ...
targeted therapies for the treatment of clinical depression.


See also

* Induced somatic stem cells


References


External links


NIH Stem Cell Information Resource
resource for stem cell research
Nature Reports Stem Cells
Background information, research advances and debates about stem cell science
UMDNJ Stem Cell and Regenerative Medicine
provides educational materials and research resources
Stem Cell Research at Johns Hopkins University
{{DEFAULTSORT:Adult Stem Cell Stem cells Biotechnology