Mesenchymal stem cell

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Mesenchymal stem cell_table_infobox_0

Mesenchymal stem cellMesenchymal stem cell_header_cell_0_0_0
DetailsMesenchymal stem cell_header_cell_0_1_0
IdentifiersMesenchymal stem cell_header_cell_0_2_0
LatinMesenchymal stem cell_header_cell_0_3_0 Cellula mesenchymatica praecursoriaMesenchymal stem cell_cell_0_3_1
MeSHMesenchymal stem cell_header_cell_0_4_0 Mesenchymal stem cell_cell_0_4_1
THMesenchymal stem cell_header_cell_0_5_0 Mesenchymal stem cell_cell_0_5_1

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 cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue). Mesenchymal stem cell_sentence_0

Structure Mesenchymal stem cell_section_0

Definition Mesenchymal stem cell_section_1

While the terms mesenchymal stem cell (MSC) and marrow stromal cell have been used interchangeably for many years, neither term is sufficiently descriptive: Mesenchymal stem cell_sentence_1

Mesenchymal stem cell_unordered_list_0

  • Mesenchyme is embryonic connective tissue that is derived from the mesoderm and that differentiates into hematopoietic and connective tissue, whereas MSCs do not differentiate into hematopoietic cells.Mesenchymal stem cell_item_0_0
  • 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.Mesenchymal stem cell_item_0_1
  • The term encompasses multipotent cells derived from other non-marrow tissues, such as placenta, umbilical cord blood, adipose tissue, adult muscle, corneal stroma or the dental pulp of deciduous (baby) teeth. The cells do not have the capacity to reconstitute an entire organ.Mesenchymal stem cell_item_0_2

Morphology Mesenchymal stem cell_section_2

Mesenchymal stem cells are characterized morphologically by a small cell body with a few cell processes that are long and thin. Mesenchymal stem cell_sentence_2

The cell body contains a large, round nucleus with a prominent nucleolus, which is surrounded by finely dispersed chromatin particles, giving the nucleus a clear appearance. Mesenchymal stem cell_sentence_3

The remainder of the cell body contains a small amount of Golgi apparatus, rough endoplasmic reticulum, mitochondria and polyribosomes. Mesenchymal stem cell_sentence_4

The cells, which are long and thin, are widely dispersed and the adjacent extracellular matrix is populated by a few reticular fibrils but is devoid of the other types of collagen fibrils. Mesenchymal stem cell_sentence_5

These distinctive morphological features of mesenchymal stem cells can be visualized label-free using live cell imaging. Mesenchymal stem cell_sentence_6

Location Mesenchymal stem cell_section_3

Bone marrow Mesenchymal stem cell_section_4

Bone marrow was the original source of MSCs, and still is the most frequently utilized. Mesenchymal stem cell_sentence_7

These bone marrow stem cells do not contribute to the formation of blood cells and so do not express the hematopoietic stem cell marker CD34. Mesenchymal stem cell_sentence_8

They are sometimes referred to as bone marrow stromal stem cells. Mesenchymal stem cell_sentence_9

Cord cells Mesenchymal stem cell_section_5

The youngest and most primitive MSCs may be obtained from umbilical cord tissue, namely Wharton's jelly and the umbilical cord blood. Mesenchymal stem cell_sentence_10

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 cells. Mesenchymal stem cell_sentence_11

The umbilical cord is available after a birth. Mesenchymal stem cell_sentence_12

It is normally discarded and poses no risk for collection. Mesenchymal stem cell_sentence_13

These MSCs may prove to be a useful source of MSCs for clinical applications due to their primitive properties and fast growth rate. Mesenchymal stem cell_sentence_14

Adipose tissue Mesenchymal stem cell_section_6

Adipose tissue is another source of MSCs and these have several advantages over bone marrow-derived MSCs. Mesenchymal stem cell_sentence_15

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. Mesenchymal stem cell_sentence_16

Molar cells Mesenchymal stem cell_section_7

The developing tooth bud of the mandibular third molar is a rich source of MSCs. Mesenchymal stem cell_sentence_17

While they are described as multipotent, it is possible that they are pluripotent. Mesenchymal stem cell_sentence_18

They eventually form enamel, dentin, blood vessels, dental pulp and nervous tissues. Mesenchymal stem cell_sentence_19

These stem cells are capable of differentiating into chondrocytes, cardiomyocytes, melanocytes, and hepatocyte‐like cells in vitro. Mesenchymal stem cell_sentence_20

Amniotic fluid Mesenchymal stem cell_section_8

Stem cells are present in amniotic fluid. Mesenchymal stem cell_sentence_21

As many as 1 in 100 cells collected during amniocentesis are pluripotent mesenchymal stem cells. Mesenchymal stem cell_sentence_22

Function Mesenchymal stem cell_section_9

Differentiation capacity Mesenchymal stem cell_section_10

MSCs have a great capacity for self-renewal while maintaining their multipotency. Mesenchymal stem cell_sentence_23

Recent work suggests that β-catenin, via regulation of EZH2, is a central molecule in maintaining the "stemness" of MSC's. Mesenchymal stem cell_sentence_24

The standard test to confirm multipotency is differentiation of the cells into osteoblasts, adipocytes and chondrocytes as well as myocytes. Mesenchymal stem cell_sentence_25

MSCs have been seen to even differentiate into neuron-like cells, but doubt remains about whether the MSC-derived neurons are functional. Mesenchymal stem cell_sentence_26

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. Mesenchymal stem cell_sentence_27

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. Mesenchymal stem cell_sentence_28

Likewise, whether this is due to a decrease in the number of MSCs or a change to the existing MSCs is not known. Mesenchymal stem cell_sentence_29

Immunomodulatory effects Mesenchymal stem cell_section_11

MSCs have an effect on innate and specific immune cells. Mesenchymal stem cell_sentence_30

MSCs produce many immunomodulatory molecules including prostaglandin E2 (PGE2), nitric oxide, indoleamine 2,3-dioxygenase (IDO), interleukin 6 (IL-6), and other surface markers such as FasL, PD-L1 and PD-L2. Mesenchymal stem cell_sentence_31

MSCs have an effect on macrophages, neutrophils, NK cells, mast cells and dendritic cells in innate immunity. Mesenchymal stem cell_sentence_32

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. Mesenchymal stem cell_sentence_33

Further, PGE2 inhibits the ability of mast cells to degranulate and produce TNF-α. Mesenchymal stem cell_sentence_34

Proliferation and cytotoxic activity of NK cells is inhibited by PGE2 and IDO. Mesenchymal stem cell_sentence_35

MSCs also reduce the expression of NK cell receptors - NKG2D, NKp44 and NKp30. Mesenchymal stem cell_sentence_36

MSCs inhibit respiratory flare and apoptosis of neutrophils by production of cytokines IL-6 and IL-8. Mesenchymal stem cell_sentence_37

Differentiation and expression of dendritic cell surface markers is inhibited by IL-6 and PGE2 of MSCs. Mesenchymal stem cell_sentence_38

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. Mesenchymal stem cell_sentence_39

MSC expresses the adhesion molecules VCAM-1 and ICAM-1, which allow T-lymphocytes to adhere to their surface. Mesenchymal stem cell_sentence_40

Then MSC can affect them by molecules which have a short half-life and their effect is in the immediate vicinity of the cell. Mesenchymal stem cell_sentence_41

These include nitric oxide, PGE2, HGF, and activation of receptor PD-1. Mesenchymal stem cell_sentence_42

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. Mesenchymal stem cell_sentence_43

MSCs also inhibit the proliferation of B-lymphocytes between G0 and G1 cell cycle phases. Mesenchymal stem cell_sentence_44

Antimicrobial properties Mesenchymal stem cell_section_12

MSCs produce several antimicrobial peptides (AMPs) including human cathelicidin LL-37, β-defensins, lipocalin 2 and hepcidin. Mesenchymal stem cell_sentence_45

These peptides, together with the enzyme indoleamine 2,3-dioxygenase (IDO), are responsible for the broad-spectrum antibacterial activity of MSCs. Mesenchymal stem cell_sentence_46

Clinical significance Mesenchymal stem cell_section_13

Mesenchymal stem cells can be activated and mobilized if needed but their efficiency, in the case of muscle repair for example, is currently quite low. Mesenchymal stem cell_sentence_47

Further studies into the mechanisms of MSC action may provide avenues for increasing their capacity for tissue repair. Mesenchymal stem cell_sentence_48

Autoimmune disease Mesenchymal stem cell_section_14

Clinical studies investigating the efficacy of mesenchymal stem cells in treating diseases are in preliminary development, particularly for understanding autoimmune diseases, graft versus host disease, Crohn's disease, multiple sclerosis, systemic lupus erythematosus and systemic sclerosis. Mesenchymal stem cell_sentence_49

As of 2014, no high-quality clinical research provides evidence of efficacy, and numerous inconsistencies and problems exist in the research methods. Mesenchymal stem cell_sentence_50

Other diseases Mesenchymal stem cell_section_15

Many of the early clinical successes using intravenous transplantation came in systemic diseases such as graft versus host disease and sepsis. Mesenchymal stem cell_sentence_51

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. Mesenchymal stem cell_sentence_52

Detection Mesenchymal stem cell_section_16

The International Society for Cellular Therapy (ISCT) has proposed a set of standards to define MSCs. Mesenchymal stem cell_sentence_53

A cell can be classified as an MSC if it shows plastic adherent properties under normal culture conditions and has a fibroblast-like morphology. Mesenchymal stem cell_sentence_54

In fact, some argue that MSCs and fibroblasts are functionally identical. Mesenchymal stem cell_sentence_55

Furthermore, MSCs can undergo osteogenic, adipogenic and chondrogenic differentiation ex vivo. Mesenchymal stem cell_sentence_56

The cultured MSCs also express on their surface CD73, CD90 and CD105, while lacking the expression of CD11b, CD14, CD19, CD34, CD45, CD79a and HLA-DR surface markers. Mesenchymal stem cell_sentence_57

Research Mesenchymal stem cell_section_17

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 cells are plated directly into cell culture plates or flasks. Mesenchymal stem cell_sentence_58

Mesenchymal stem cells, but not red blood cells or haematopoetic progenitors, are adherent to tissue culture plastic within 24 to 48 hours. Mesenchymal stem cell_sentence_59

However, at least one publication has identified a population of non-adherent MSCs that are not obtained by the direct-plating technique. Mesenchymal stem cell_sentence_60

Other flow cytometry-based methods allow the sorting of bone marrow cells for specific surface markers, such as STRO-1. Mesenchymal stem cell_sentence_61

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. Mesenchymal stem cell_sentence_62

Methods of immunodepletion using such techniques as MACS have also been used in the negative selection of MSCs. Mesenchymal stem cell_sentence_63

The supplementation of basal media with fetal bovine serum or human platelet lysate is common in MSC culture. Mesenchymal stem cell_sentence_64

Prior to the use of platelet lysates for MSC culture, the pathogen inactivation process is recommended to prevent pathogen transmission. Mesenchymal stem cell_sentence_65

New research titled Transplantation of human ESC-derived mesenchymal stem cell spheroids ameliorates spontaneous osteoarthritis in rhesus macaques Mesenchymal stem cell_sentence_66

History Mesenchymal stem cell_section_18

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 that develops into different types of blood cells. Mesenchymal stem cell_sentence_67

Scientists Ernest A. McCulloch and James E. Till first revealed the clonal nature of marrow cells in the 1960s. Mesenchymal stem cell_sentence_68

An ex vivo assay for examining the clonogenic potential of multipotent marrow cells was later reported in the 1970s by Friedenstein and colleagues. Mesenchymal stem cell_sentence_69

In this assay system, stromal cells were referred to as colony-forming unit-fibroblasts (CFU-f). Mesenchymal stem cell_sentence_70

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. Mesenchymal stem cell_sentence_71

Since then, more than 200 clinical trials have been started. Mesenchymal stem cell_sentence_72

However, most are still in the safety stage of testing. Mesenchymal stem cell_sentence_73

Subsequent experimentation revealed the plasticity of marrow cells and how their fate is determined by environmental cues. Mesenchymal stem cell_sentence_74

Culturing marrow stromal cells in the presence of osteogenic stimuli such as ascorbic acid, inorganic phosphate and dexamethasone could promote their differentiation into osteoblasts. Mesenchymal stem cell_sentence_75

In contrast, the addition of transforming growth factor-beta (TGF-b) could induce chondrogenic markers. Mesenchymal stem cell_sentence_76

See also Mesenchymal stem cell_section_19

Mesenchymal stem cell_unordered_list_1

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: stem cell.