Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling 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 ...
stromal cell
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa ...
s that can
differentiate into a variety of cell types, including
osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
s (bone cells),
chondrocytes (cartilage cells),
myocyte
A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
s (muscle cells) and
adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
s (fat cells which give rise to
marrow adipose tissue
Bone marrow adipose tissue (BMAT), sometimes referred to as marrow adipose tissue (MAT), is a type of fat deposit in bone marrow. It increases in states of low bone density -osteoporosis, anorexia nervosa/ caloric restriction, skeletal unweigh ...
).
Structure
Definition
While the terms ''mesenchymal stem cell'' (MSC) and ''marrow stromal cell'' have been used interchangeably for many years, neither term is sufficiently descriptive:
*
Mesenchyme
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...
is
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
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
that is derived from the
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 E ...
and that differentiates into
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. ...
and connective tissue, whereas MSCs do not differentiate into hematopoietic cells.
*
Stromal cells are connective tissue cells that form the supportive structure in which the functional cells of the tissue reside. While this is an accurate description for one function of MSCs, the term fails to convey the relatively recently discovered roles of MSCs in the repair of tissue.
* The term encompasses multipotent cells derived from other non-
marrow tissues, such as
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 ...
,
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 physiologic ...
blood,
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 e ...
, adult
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
,
corneal stroma
The stroma of the cornea (or substantia propria) is a fibrous, tough, unyielding, perfectly transparent and the thickest layer of the cornea of the eye. It is between Bowman's membrane anteriorly, and Descemet's membrane posteriorly.
At its cent ...
or the dental pulp of
deciduous
In the fields of horticulture and Botany, the term ''deciduous'' () means "falling off at maturity" and "tending to fall off", in reference to trees and shrubs that seasonally shed leaves, usually in the autumn; to the shedding of petals, aft ...
(baby) teeth.
The cells do not have the capacity to reconstitute an entire organ.
Morphology
![Human mesenchymal stem cells](https://upload.wikimedia.org/wikipedia/commons/0/04/Human_mesenchymal_stem_cells.gif)
Mesenchymal stem cells are characterized morphologically by a small
cell body with a few cell processes that are long and thin. The cell body contains a large, round
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
with a prominent
nucleolus
The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of sig ...
, which is surrounded by finely dispersed
chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
particles, giving the nucleus a clear appearance. The remainder of the cell body contains a small amount of
Golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
,
rough endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
,
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
and
polyribosomes
A polyribosome (or polysome or ergosome) is a group of ribosomes bound to an Messenger RNA, mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translation (biology) ...
. The cells, which are long and thin, are widely dispersed and the adjacent
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 populated by a few
reticular
In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...
fibrils but is devoid of the other types of
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
fibrils.
These distinctive morphological features of mesenchymal stem cells can be visualized label-free using live cell imaging.
Location
Bone marrow
Bone marrow was the original source of MSCs,
and still is the most frequently utilized. These bone marrow stem cells do not contribute to the formation of blood cells and so do not express the
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 ...
marker
CD34
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.
CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...
. They are sometimes referred to as ''bone marrow stromal stem cells''.
Cord cells
The youngest and most primitive MSCs may be obtained from umbilical cord tissue, namely
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 ...
and the 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 ...
. However MSCs are found in much higher concentration in the Wharton's jelly compared to cord blood, which is a rich source of
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. The umbilical cord is available after a birth. It is normally discarded and poses no risk for collection. These MSCs may prove to be a useful source of MSCs for clinical applications due to their primitive properties and fast growth rate.
and these have several advantages over bone marrow-derived MSCs. Adipose tissue-derived MSCs (AdMSCs), in addition to being easier and safer to isolate than bone marrow-derived MSCs, can be obtained in larger quantities.
Molar cells
The developing tooth bud of the mandibular third molar is a rich source of MSCs. While they are described as multipotent, it is possible that they are pluripotent. They eventually form enamel, dentin, blood vessels, dental pulp and nervous tissues. These stem cells are capable of differentiating into
chondrocytes,
cardiomyocyte
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...
s,
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, 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, ...
‐like cells ''in vitro''.
Amniotic fluid
Stem cells are present 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 ...
. As many as 1 in 100 cells collected during
amniocentesis
Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is ne ...
are pluripotent mesenchymal stem cells.
Function
Differentiation capacity
MSCs have a great capacity for self-renewal while maintaining their multipotency. Recent work suggests that β-catenin, via regulation of EZH2, is a central molecule in maintaining the "stemness" of MSC's. The standard test to confirm multipotency is differentiation of the cells into osteoblasts, adipocytes and chondrocytes as well as myocytes.
MSCs have been seen to even differentiate into neuron-like cells, but doubt remains about whether the MSC-derived neurons are functional. The degree to which the culture will differentiate varies among individuals and how differentiation is induced, e.g., chemical vs. mechanical; and it is not clear whether this variation is due to a different amount of "true" progenitor cells in the culture or variable differentiation capacities of individuals' progenitors. The capacity of cells to
proliferate and
differentiate is known to decrease with the age of the donor, as well as the time in culture. Likewise, whether this is due to a decrease in the number of MSCs or a change to the existing MSCs is not known.
Immunomodulatory effects
MSCs have an effect on innate and specific immune cells, and research has shown an ability to suppress tumor growth. MSCs produce many immunomodulatory molecules including
prostaglandin E2
Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and ...
(PGE2),
nitric oxide
Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...
,
indoleamine 2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO ) is a heme-containing enzyme physiologically expressed in a number of tissues and cells, such as the small intestine, lungs, female genital tract or placenta. In humans is encoded by the ''IDO1' ...
(IDO),
interleukin 6
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene.
In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...
(IL-6), and other surface markers such as
FasL
Fas ligand (FasL or CD95L or CD178) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regula ...
,
PD-L1
Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the ''CD274'' gene.
Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protei ...
and
PD-L2.
MSCs have an effect on macrophages, neutrophils, NK cells, mast cells and dendritic cells in innate immunity. MSCs are able to migrate to the site of injury, where they polarize through PGE2 macrophages in M2 phenotype which is characterized by an anti-inflammatory effect. Further, PGE2 inhibits the ability of mast cells to degranulate and produce TNF-α. Proliferation and cytotoxic activity of NK cells is inhibited by PGE2 and IDO. MSCs also reduce the expression of NK cell receptors - NKG2D, NKp44 and NKp30. MSCs inhibit respiratory flare and apoptosis of neutrophils by production of cytokines IL-6 and IL-8. Differentiation and expression of dendritic cell surface markers is inhibited by IL-6 and PGE2 of MSCs. The immunosuppressive effects of MSC also depend on IL-10, but it is not certain whether they produce it alone, or only stimulate other cells to produce it.
MSC expresses the adhesion molecules VCAM-1 and ICAM-1, which allow T-lymphocytes to adhere to their surface. Then MSC can affect them by molecules which have a short half-life and their effect is in the immediate vicinity of the cell.
These include nitric oxide, PGE2, HGF, and activation of receptor PD-1.
MSCs reduce T cell proliferation between G0 and G1 cell cycle phases and decrease the expression of IFNγ of Th1 cells while increasing the expression of IL-4 of Th2 cells. MSCs also inhibit the proliferation of B-lymphocytes between G0 and G1 cell cycle phases.
Antimicrobial properties
MSCs produce several
antimicrobial peptides
Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for a ...
(AMPs) including human
cathelicidin LL-37,
β-defensins,
lipocalin 2 and
hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.
During conditions in which the hepcidin level is abnormally high, such as inflammation, se ...
. These peptides, together with the enzyme
indoleamine 2,3-dioxygenase
Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO ) is a heme-containing enzyme physiologically expressed in a number of tissues and cells, such as the small intestine, lungs, female genital tract or placenta. In humans is encoded by the ''IDO1' ...
(IDO), are responsible for the broad-spectrum antibacterial activity of MSCs.
Clinical significance
![Typical gross appearance of a tubular cartilaginous construct engineered from amniotic mesenchymal stem cells](https://upload.wikimedia.org/wikipedia/commons/8/8d/Typical_gross_appearance_of_a_tubular_cartilaginous_construct_engineered_from_amniotic_mesenchymal_stem_cells..jpg)
Mesenchymal stem cells can be activated and
mobilized
Mobilization is the act of assembling and readying military troops and supplies for war. The word ''mobilization'' was first used in a military context in the 1850s to describe the preparation of the Prussian Army. Mobilization theories and ...
if needed but their efficiency, in the case of muscle repair for example, is currently quite low. Further studies into the mechanisms of MSC action may provide avenues for increasing their capacity for tissue repair.
Autoimmune disease
Clinical studies investigating the efficacy of mesenchymal stem cells in treating diseases are in preliminary development, particularly for understanding
autoimmune disease
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s,
graft versus host disease
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donor's immune system which remain wit ...
,
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 ...
,
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
,
systemic lupus erythematosus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
and
systemic sclerosis
Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two ...
.
As of 2014, no high-quality clinical research provides evidence of efficacy, and numerous inconsistencies and problems exist in the research methods.
[
]
Other diseases
Many of the early clinical successes using intravenous transplantation came in systemic diseases such as graft versus host disease
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donor's immune system which remain wit ...
and sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. 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.
Detection
The International Society for Cellular Therapy (ISCT) has proposed a set of standards to define MSCs. A cell can be classified as an MSC if it shows plastic adherent properties under normal culture conditions and has a fibroblast-like morphology. In fact, some argue that MSCs and fibroblasts are functionally identical. Furthermore, MSCs can undergo osteogenic, adipogenic and chondrogenic differentiation ''ex vivo''. The cultured MSCs also express on their surface CD73
5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 (cluster of differentiation 73), is an enzyme that in humans is encoded by the ''NT5E'' gene. CD73 commonly serves to convert AMP to adenosine.
Transcription factor bindi ...
, CD90
Thy-1 or CD90 (Cluster of Differentiation 90) is a 25–37 k Da heavily N-glycosylated, glycophosphatidylinositol (GPI) anchored conserved cell surface protein with a single V-like immunoglobulin domain, originally discovered as a thymocyte antig ...
and 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 ...
, while lacking the expression of CD11b
Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as ''macrophage-1 antigen'' (Mac-1) or ''complement receptor 3'' (CR3). ITGAM is also known as CR3A, and cluster of dif ...
, CD14
CD14 (cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP).
...
, CD19, CD34
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.
CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...
, CD45
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the ''PTPRC'' gene. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leuko ...
, CD79a
Cluster of differentiation CD79A also known as B-cell antigen receptor complex-associated protein alpha chain and MB-1 membrane glycoprotein, is a protein that in humans is encoded by the CD79A gene.
The CD79a protein together with the related C ...
and HLA-DR
HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR (Human Leukocyte Antigen – DR isotype) and peptide, generally between 9 and 30 amino acids in ...
surface markers.
Research
The majority of modern culture techniques still take a colony-forming unit-fibroblasts (CFU-F) approach, where raw unpurified bone marrow or ficoll-purified bone marrow mononuclear cell
In immunology, agranulocytes (also known as nongranulocytes or mononuclear leukocytes) are one of the two types of leukocytes (white blood cells), the other type being granulocytes. Agranular cells are noted by the absence of Granule (cell biol ...
s are plated directly into cell culture
Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
plates or flasks. Mesenchymal stem cells, but not red blood cells or haematopoetic progenitors, are adherent to tissue culture plastic within 24 to 48 hours. However, at least one publication has identified a population of non-adherent MSCs that are not obtained by the direct-plating technique.
Other flow cytometry
Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles.
In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...
-based methods allow the sorting of bone marrow cells for specific surface markers, such as STRO-1. STRO-1+ cells are generally more homogenous and have higher rates of adherence and higher rates of proliferation, but the exact differences between STRO-1+ cells and MSCs are not clear.
Methods of immunodepletion using such techniques as MACS have also been used in the negative selection of MSCs.
The supplementation of basal media with fetal bovine serum
Fetal bovine serum (FBS) is derived from the blood drawn from a bovine fetus via a closed system of collection at the slaughterhouse. Fetal bovine serum is the most widely used serum-supplement for the in vitro cell culture of eukaryotic cells. Th ...
or human platelet lysate Human platelet lysate (or hPL) is a substitute supplement for fetal bovine serum (FBS) in experimental and clinical cell culture. It is a turbid, light-yellow liquid that is obtained from human blood platelets after freeze/thaw cycle(s). The freeze/ ...
is common in MSC culture.
Prior to the use of platelet lysates for MSC culture, the pathogen inactivation process is recommended to prevent pathogen transmission.
New research titled Transplantation of human ESC-derived mesenchymal stem cell spheroids ameliorates spontaneous osteoarthritis in rhesus macaques Various chemicals and methods including low level laser irradiation have been used to increase proliferation of stem cell.
History
In 1924, Russian-born morphologist Alexander A. Maximov (russian: Александр Александрович Максимов); used extensive histological findings to identify a singular type of precursor cell within mesenchyme
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...
that develops into different types of blood cells.
Scientists Ernest A. McCulloch and James E. Till first revealed the clonal nature of marrow cells in the 1960s. An ''ex vivo
''Ex vivo'' (Latin: "out of the living") literally means that which takes place outside an organism. In science, ''ex vivo'' refers to experimentation or measurements done in or on tissue from an organism in an external environment with minimal ...
'' assay for examining the clonogenic potential of multipotent marrow cells was later reported in the 1970s by Friedenstein and colleagues. In this assay system, stromal cells were referred to as colony-forming unit-fibroblasts (CFU-f).
The first clinical trials of MSCs were completed in 1995 when a group of 15 patients were injected with cultured MSCs to test the safety of the treatment. Since then, more than 200 clinical trials have been started. However, most are still in the safety stage of testing.
Subsequent experimentation revealed the plasticity of marrow cells and how their fate is determined by environmental cues. Culturing marrow stromal cells in the presence of osteogenic stimuli such as ascorbic acid
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
, inorganic phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phosph ...
and dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...
could promote their differentiation into osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
s. In contrast, the addition of transforming growth factor-beta (TGF-b) could induce chondrogenic markers.
Controversies
More recently, there has been some debate over the use of the term "mesenchymal stem cells" and what constitutes the most scientifically correct meaning for the MSC acronym. Most mesenchymal cell or "MSC" preps only contain a minority fraction of true multipotent stem cells, while most cells are instead stromal in nature. One of the pioneers in the MSC field, Dr. Arnold Caplan, has proposed re-naming MSCs to mean "medicinal signaling cells." Within the stem cell field MSC has most commonly now come to refer to "mesenchymal stromal/stem cells" because of the heterogeneous nature of the cellular preparations.
There is also growing concern about the marketing and injection of MSCs and mesenchymal stem cells into patients by for-profit clinics that lack rigorous data to back up these clinical uses.
See also
* 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 ...
*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 ...
* Intramembranous ossification
Intramembranous ossification is one of the two essential processes during fetal development of the gnathostome (excluding chondrichthyans such as sharks) skeletal system by which rudimentary bone tissue is created.
Intramembranous ossification is a ...
* Mesenchyme
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...
* 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 ...
* Cord lining Cord lining, cord tissue, or umbilical cord lining membrane, is the outermost layer of the umbilical cord. As the umbilical cord itself is an extension of the placenta, the umbilical cord lining membrane is an extension of the amniotic membrane cove ...
* Marrow Adipose Tissue (MAT)
*List of human cell types derived from the germ layers
This is a list of cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm.
Cells derived from ectoderm
Surface ectoderm Skin
* Trichocyte
* Keratinocyte
Anterior pituitary
* Gonadotrope
* Corticotro ...
References
Further reading
*
External links
* scientist-reviewed and not too technical
*
{{Authority control
Stem cells