Factors secreted by MSCs in culture
Cultured MSCs express low levels of MHC Class I and are MHC Class II−, CD40−, and CD86−, suggesting these cells would not elicit an immune response [1,2]. The immuno-modulatory capacities of MSCs have been demonstrated by several independent research groups, both in vitro and in vivo, in animal models and in humans [3,4,5]. The immuno-modulatory functions of MSCs were first demonstrated in their ability to suppress in vitro proliferation of T lymphocytes . Since then, several studies have shown that MSCs can modulate many cell types involved in the immune response in vitro. These include natural killer (NK) cells, B lymphocytes and dendritic cells [3,4,5]. The inhibition of T cell proliferation has been shown to be transient, whereby the removal of MSCs reinstates the T cell proliferative state . T cell proliferation inhibition by MSCs is also known to act independently of cell-cell contact with the suppressive effect attributed to the secretion of either Transforming growth factor-β (TGF-β), Hepatocyte growth factor (HGF), Prostaglandin E2 (PGE2), Indoleamine 2,3-dioxygenase (IDO), Nitrous Oxide (NO) or Interluekin-10 (IL-10) [7,8]. This inhibition of proliferation is observed in both autologous and allogeneic responder cells . By demonstrating that this action is not HLA restricted, MSCs are shown to be a good candidate therapy for use allogeneically . MSCs interfere with functioning, differentiation and maturation of dendritic cells. Again, this is not dependent on cell-cell contact with the MSCs, but on soluble factors secreted by the MSCs including IL-6, IL-10, macrophage colony-stimulating factor (M-CSF) and PGE2 . The inhibition of B cells by MSCs is dependent on inflammatory conditions . MSCs in the presence of IFNγ reduce B cell proliferation via the induction of IDO . To inhibit NK cell proliferation, MSCs have been shown to require activation with either IL-2 or IL-15 [14,15].
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