| Over the last 30 years allogeneic bone marrow transplantation (Allo-BMT) has become an accepted curative therapy for a variety of malignant hematopoietic diseases, immunodeficiencies, and disease cause by genetically abnormal hematopoietic progenitor cells. To date, the chief obstacle to the deployment of this treatment in other than life-threatening conditions is graft-versus-host disease (GVHD), and in particular acute GVHD, which is most severe in patients receiving matched unrelated donor transplants. The immunosuppressive drugs and T-cell depletion is effective at controlling GVHD, but these regimens can lead to serious complications from infection and an increased risk of leukemia relapse after Allo-BMT..Many researchers have therefore sought to develop techniques to prevent GVHD that avoid the complications incurred by immunosuppression.Mesenchymal stem cells (MSC) are multipotent precursors present in bone marrow, capable of differentiating into osteoblasts, adipocytes, and myoblasts. Some studies in NOD/SCID mice indicate that co-transplantation of MSC enhances engraftment of human hematopoietic cells in the bone marrow of NOD/SCID mice. MSC can produce a variety of cytokines that promote the homing or proliferation and differentiation of hematopoietic cells, and accordingly play important roles in promoting hematopoietic recovery. Moreover, MSC are poor antigen-presenting cells and do not express MHC class II or co-stimulatory molecules. These cells also exhibit immunoregulatory properties in vitro as demonstrated by their ability to suppress the mixed lymphocyte reaction (MLR). In a baboon skin graft rejection model, in vivo infusion of MSC resulted in prolonged skin graft survival in comparison with control animals not treated with MSC.The aim of this study was investigate the immunoregulatory effect of murine MSC by coinfusion of bone marrow cells and culture-expanded MSC in allogeneic murine GVHD models. Murine bone marrow MSC were isolated and cultured and then their phenotye and differentiation function were identified with FCM and histochemical technique.It was established that GVHD models in allogeneic murine bone marrowtransplantation by coinfusion of donor bone marrow cells and donor splenocytes. Finally, the immunoregulatory effect of murine MSC was observed by coinfusion of bone marrow cells and culture-expanded MSC in murine GVHD models. The results showed that the morphology of MSC became gradually homogeneous with the passage culture of cells. After passage 4, the marker of Sca-1, CD29, CD44 and CD 105 were highly expressed, however, CD34 and CD45, the specific marker of hematopoietic and endothelial cells, could hardly be identified. The isolated MSC differentiated into adipocytes and osteoblasts in specific induction culture system. All mice injected with 107 marrow cells and more than 5X 106 splenocytes developed acute GVHD and died, but injected with the more splenocytes appeared the severer and earlier GVHD. Co-infusion expanded host-drived MSC (5X104) with bone marrow cells (1X107) and spleen cells (5 X 106) or Co-infusion expanded donor-drived MSC (1 X 106) with bone marrow cells (1 X 107) and spleen cells (5 X 107) was completed . There was no statistic difference between the MSC co-infusion group and the GVHD model group. However, the severer GVHD in the MSC co-infusion group was observed. Our results indicated: (1) Murine MSC could be attained by cultured murine marrow cells with bone fragments. (2) GVHD models of allogeneic murine bone marrow transplantation were established by infusion of different spleen cells. (3) Co-infusion of culture-expanded murine MSC and HST(donor-derived MSC 1 X 106 and spleen cells 5 X107, receiver-derived MSC 5X104and spleen cells 5X106) aggravated extent of acute GVHD. It was associated with the little number of murine MSC and the poor ability of murine MSC homing to bone marrow. It seems that in vivo immunoregulatory effort was constrained by many factors. Therefore, further studies are required to carry on in this area. |
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