Mesenchymal stem cells (MSC) mostly surround the vasculature system of bone marrow (BM). MSC have been shown to exhibit immune suppressive properties. Since MSC express MHC Class II antigen, the question is whether these cells can act as APC. To this end, we hypothesize that MSC have the ability to present non-self antigens while acting as immune modulators. These dual roles of MSC prevent exacerbated inflammatory responses in the BM, thereby preventing hematopoietic dysfunction.
A ‘dampened’ immune response in BM during insults by foreign agents could cause protection of the barrier that separates BM cavity with the periphery. The phagocytic role of MSC was shown by confocal microscopy and fluoresbrite plain YG 1.0-micron microspheres. APC property was demonstrated by challenging MSC with C. albicans (pulsed MSC), followed by exposure to CD4+ cells. The latter was obtained by immunoselection from peripheral blood mononuclear cells (PBMC) cultured for 5 days with C. albicans (10 mg/ml). Proliferation of the CD4+ cells (3H-thymidine incorporation and cell counts) proved APC properties of MSC, at efficiency comparable to macrophages. Overall, the studies show that the window between APC function and the period at which MSC could become immune suppressive is critical, since activated T-cells could destroy the endothelial barrier between BM and lymphatics/peripheral circulation. These studies show that MSC could be key cells in regulating immune responses in BM, and thereby protect BM from failure.