dc.description.abstract | Graft versus host disease (GVHD) is a significant complication that can occur after allogeneic transplants, particularly bone marrow transplantation. Mesenchymal stem cells (MSCs) have garnered attention for their potential in treating immune-related diseases such as GVHD because of their immunosuppressive properties. In this study, I aimed to evaluate the efficacy of various types of human MSCs (hMSCs) in suppressing GVHD, and the optimal cell culture environment (biomaterials) was investigated for GVHD treatment by hMSCs. The osteogenic differentiation of hMSCs was conducted to generate osteoblasts, which simulated the bone cell environment commonly affected in GVHD scenarios. Subsequently, human amniotic fluid stem cells (hAFSCs), human adipose-derived stem cells (hADSCs), and human pluripotent stem cells (hiPSCs, HPS0077)-derived MSCs were treated with allogeneic mononuclear cells. Following this treatment, live and dead staining of hMSCs was conducted to assess their viability and response to allogeneic mononuclear cells. These cells were subjected to allogeneic mononuclear cell treatment to evaluate their ability to suppress inflammation reactions associated with GVHD. hiPSC-derived osteoblasts with several hMSCs (hAFSCs, hADSCs, and hiPSC-derived MSCs) were also treated with allogenic mononuclear cells and were evaluated the viability of osteoblasts and the immune response by the mononuclear cells. Results indicated that hADSCs, hAFSCs, and hiPSCs-derived MSCs could suppress inflammation reactions on hMSCs as well as hiPSC-derived osteoblasts, which were induced by allogenic mononuclear cells. Furthermore, the effect of extracellular matrix (ECM) proteins (laminin-521, recombinant vitronectin, and Matrigel) on the survival of hMSCs and hiPSC-derived osteoblasts was evaluated in the presence of allogeneic mononuclear cells. hMSCs and hiPSC-derived osteoblasts cultured on Matrigel-coated dishs exhibited higher viability than those cultured on other ECM-coated dishs after treatment with allogeneic mononuclear cells. Notably, hAFSCs and hiPSCs-derived MSCs cultured on LN521 demonstrated enhanced immune tolerance, suggesting the potential for application in preventing immune reactions by the cells. The study highlights the future potential of these immunosuppressive effects of hMSCs, particularly hiPSC-derived MSCs, in treating other immune-related diseases beyond GVHD. Overall, the findings underscore the promising therapeutic potential of various hMSCs and the importance of considering the cell culture environment in optimizing their efficacy for GVHD treatment. | en_US |