Abstract
Recent progress in regenerative medicine has enabled the utilization of pluripotent stem cells (PSCs) as the resource of therapeutic cells/tissue. However, immune suppression is still needed when the donor–recipient combination is allogeneic. We have reported previously that mouse PSCs-derived immunosuppressive cells contribute to prolonged survival of grafts derived from the same mouse PSCs in allogeneic recipients. For its clinical application, a preclinical study using non-human primates such as common marmoset must be performed. In this study, we established the induction protocol of immunosuppressive cells from common marmoset ES cells. Although similar immunosuppressive macrophages could not be induced by same protocol as that for mouse PSCs, we employed an inhibitor for histone methyltransferase, DZNep, and succeeded to induce them. The DZNep-treated macrophage-like cells expressed several immunosuppressive molecules and significantly inhibited allogeneic mixed lymphocyte reaction. The immunosuppressive cells from non-human primate ESCs will help to establish an immunoregulating strategy in regenerative medicine using PSCs.
Highlights
Pluripotent stem cells (PSCs) including induced pluripotent stem cells and embryonic stem cells (ESCs) provide new opportunities in regenerative medicine to generate grafts for transplantation
We introduce a culture protocol to differentiate macrophage-like cells with immunosuppressive functions from common marmoset ES cells (CMESCs)
For mouse PSCs differentiation, feeder cells are commonly used in induction protocols[32,33], since the widely-used feeder cells are from mouse-origin
Summary
Pluripotent stem cells (PSCs) including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) provide new opportunities in regenerative medicine to generate grafts for transplantation. Transplantation of allogeneic PSCs-derived tissues still requires immune-suppressive therapy. Cumulative side effects, such as increased risks of malignant neoplasia and infection For these reasons, alternative therapeutic strategies are expected to induce immune suppression that is more specific for transplanted organs. It has been reported that various kinds of immunosuppressive cells, including immunosuppressive macrophages[9], regulatory T cells[10], NKT cells[11], were effective to promote tolerance in allogeneic transplantation. There are few reports about immune regulation by cell therapy in transplantation using PSCs-derived grafts
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