Abstract
Donor-specific immunological tolerance using high doses of bone marrow cells (BMCs) has been demonstrated in mixed chimerism-based tolerance induction protocols; however, the development of graft versus host disease remains a risk. Here, we demonstrate that the co-infusion of limited numbers of donor unfractionated BMCs with human amnion-derived multipotent progenitor cells (AMPs) 7 days post–allograft transplantation facilitates macrochimerism induction and graft tolerance in a mouse skin transplantation model. AMPs + BMCs co-infusion with minimal conditioning led to stable, mixed, multilineage lymphoid and myeloid macrochimerism, deletion of donor-reactive T cells, expansion of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and long-term allograft survival (>300 days). Based on these findings, we speculate that AMPs maybe a pro-tolerogenic cellular therapeutic that could have clinical efficacy for both solid organ and hematopoietic stem cell transplant applications.
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