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I.R.F. / Aging news / General / 11021801

Mesenchymal Stem Cells (MSCs)
Posted on: February 18, 2011

Mesenchymal stem cells (MSCs) were first characterized by Friedenstein and colleagues, who identified an adherent, fibroblast-like population in the adult bone marrow that could regenerate rudiments of bone in vivo. Since then, MSCs have also been isolated from other tissues, including adipose, cord blood, and fetal liver, blood, bone marrow and lung.

Mesenchymal stem cells are rare noncycling cells in the human bone marrow. Positive selection using antibodies that recognize marrow fibroblastic cells enrich for a discrete subpopulation of colony forming cells that retain the capacity to differentiate into adipose tissue, cartilage and bone in vitro.

Due to the rarity of the cells in bone marrow and the lack of a definitive marker that specifically isolates MSCs, the cells are commonly isolated by adherence to plastic and consecutive passage in tissue culture. MSCs may be expanded several fold in vitro, for instance after aspiration of bone marrow. After expansion, they can be used for in vitro research, or clinical application.

Whether culture-expanded MSCs differ from their in vivo progeny remains uncertain, as proliferation on plastic surfaces could induce both phenotypic and functional changes. Certain subtypes of MSCs may also have a survival advantage in culture. Even single cell-derived clones of MSCs vary in their gene expression, differentiative capacity, expansion potential and phenotype.

The definition of MSCs generated ex vivo is a composite of morphological, phenotypical and functional characteristics. MSCs stain negative by flow cytometry for haematopoietic markers CD34, CD45 and CD14 and positive for CD29, CD73, CD90, CD105 and CD166. Addition of exogenous factors to the growth medium induces MSCs to differentiate. It remains to be established if MSCs are true stem cells.

Regeneration and maintenance of a whole tissue compartment has not been shown by transplantation of MSCs at a single cell level - a feature characteristic of a true stem cell. However, MSCs are clearly multipotent in vivo. After injection into newborn mice or infusion in utero, the cells engraft in multiple organs and demonstrate site-specific differentiation.

MSCs can be detected in low levels in numerous tissues following intravenous infusion and preferentially home to sites of injury. In experimental animal models, MSCs not only regenerate tissues of mesenchymal lineages, such as intervertebral disc cartilage, bone, cardiomyocytes, and knee joint repair following menisectomy, but also differentiate into cells derived from other embryonic layers, including neurones, and epithelia in skin, lung, liver, intestine, kidney and spleen. MSCs constitutively secrete cytokines important for haematopoiesis and promote engraftment of haematopoietic stem cells in experimental animal models. The enhancing effect is most prominent when the dose of haematopoietic cells is limiting.

Mesenchymal stem cells have been proposed to have immunosuppressive properties and reduce inflammation. Human MSCs suppress lymphocyte alloreactivity in vitro in mixed lymphocyte cultures (MLC), through human leucocyte antigen (HLA)-independent mechanisms.

Intravenous administration of MSCs improves the outcome of renal, neural and lung injury in experimental animal models mainly through paracrine effects and a shift from the production of pro-inflammatory to anti-inflammatory cytokines at the site of injury.

Mesenchymal stem cells are one of the few normal cells that have so far been produced in large quantities needed for therapeutic development.

Preliminary data suggest that the cells have properties that allow for transplantation across major histocompatibility complex (MHC) barriers. The ability to home to damaged tissue suggests that MSCs may be used for cartilage and bone repair. They may also be used for chemotherapy-induced toxicity such as radiation gastroenteritis and haemorrhagic cystitis. The immunomodulatory effects of MSCs may be used to repair tissue damage caused by the immune system in autoimmune-induced inflammatory bowel disease such as Crohn's disease and ulcerous colitis, graft-versus-host disease (GVHD) of the gut, liver and skin after allogeneic haematopoietic stem cell transplantation (HSCT) and to prevent rejection of organ transplants.

Source: K. Le Blanc & O. Ringde; Immunomodulation by mesenchymal stem cells and clinical experience; Journal of Internal Medicine 2007; 262; 509-525; doi: 10.1111/j.1365-2796.2007.01844.x
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