title: Amnion-derived multipotent progenitor cells support allograft tolerance induction.
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 (T(regs)) 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.
authors: Department of Regenerative Medicine, Operational and Undersea Medicine Directorate at the Naval Medical Research Center, Silver Spring, MD, USA.
authors: K
authors: K
authors: Anam
authors: Y
authors: Y
authors: Lazdun
authors: P M
authors: PM
authors: Davis
authors: R A
authors: RA
authors: Banas
authors: E A
authors: EA
authors: Elster
authors: T A
authors: TA
authors: Davis
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D016038:Skin Transplantation / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous