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リエゾンラボ研究会
発表内容

Title:
New immunosuppressive therapy using pluripotent stem cells

Ken-ichiro Seino, M.D., Ph.D.
Division of immunobiology Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.

Abstract:
Objective:
The promise for cell replacement therapy using pluripotent stem cells (PSCs) as a donor source has increased. However, when non-self derived PSCs were used, immune suppression should be required. In this study, we examined a concept that some immunosuppressive cells could be induced from PSCs and those cells could prevent the allogeneic immune rejection of the PSCs-based transplantation. Materials and methods: We generated iPSCs from mouse fibroblasts by introducing Yamanaka four transcription factors. The iPSCs were differentiated on OP9 feeder cells and with some cytokines including GM-CSF. We could obtain macrophage-like cells which firmly adhered to the bacteriologic petri dish surface by a prolonged culture with IL-4 and addition of LPS. We examined their effect on allogeneic T cell responses.Results: The differentiated cells expressed molecules such as CD45, CD11b, CD11c, or F4/80, but not Gr-1, MHC class I, nor II. They also expressed some immunosuppressive molecules such as arginase I and Nos2. When added the cells to allogeneic mixed lymphocyte reaction (MLR), they efficiently suppressed allogeneic T cell proliferative response. When the cells injected to recipients of allogeneic transplantation, they significantly prolonged the survival of allogeneic grafts.Conclusion: We successfully induced regulatory macrophage-like cells from mouse iPSCs that can contribute to suppress allogeneic T cell immune responses. These results suggst a new insight for development of an immune-regulatory strategy in cell replacement therapy using PSCs.