Immunoregulatory Effect Of Mouse Bone Marrow-derived Mesenchymal Progenitor Cells

In addition to hematopoietic stem cells, bone marrow contains a population of rare progenitor cells capable of differentiating into osteoblasts, chondrocytes, adipocytes, myobiasts and hematopoiesis supporting stromal cells. These cells, referred to as mesenchymal stem/progenitor cells (MSC/MPC), can be purified and culture expanded from animals and humans by cycling adherent marrow monocytes after density-centrifugation. However, similar methods are not successful in culruring MFC from adult mouse bone marrow and little is known about the cellular biology of mouse MFC. Using bone marrow conditioned medium combined with basic fibroblast growth factor (bFGF), we cultured a relatively homogenous population of MFC from mouse bone marrow which uniformly expressed stem cell antigen-1 (Sca-1), CD29, CD44, c-kit and CD105, while negative for CD45, CD31 and CD34. In vitrodifferentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic, osteogenic, and chondrogenic lineages. Most important, immunophenotype analysis demonstrated that MFC did not express MHC class II as well as T-cell costimulatory molecules CD80 and CD86. consistent with further investigation showing that MFC failed to elicit a proliferative response from allogeneic lymphocytes. Moreover, when allogeneic MFC were added to T-cell stimulated by allogeneic lymphocytes or potent T-cell mitogen concanavalin-A (ConA), a significant reduction of T-cell proliferation was observed. This suppression was not MHC restricted, since MFC from third party donors were similarly suppressive as MFC matched to stimulator ceils in the MLR. The in vivo immunoregulatory effect was investigated using an allogeneic skin graft model. When 2xl06 donor-derived (male C57BL/6 mice) MFC were transfused intravenously into the irradiated recipient (BALB/c mice) at the same time of skin engraftment, a limited prolonged graft survival was observed. However, there was no statistic difference between the MFC transfusion group and the irradiatedcontrol. The transfused cells were indeed implanted into the recipient's bone marrow according to the PCR technique. In conclusion, our data demonstrated that primary cultured mouse bone marrow MFC could suppress T lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli in vitro. It seems that the in vivo immunoregulatory effect was constrained by many factors in spite of the striking immunosuppressive capacity of MFC in vitro. Studies are required to carry out to further investigate this area.