Amnion-derived multipotent progenitor cells support allograft tolerance induction

Am J Transplant. 2013 Jun;13(6):1416-28. doi: 10.1111/ajt.12252. Epub 2013 May 7.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amnion / cytology*
  • Animals
  • Disease Models, Animal
  • Female
  • Graft Survival / immunology*
  • Immunity, Cellular*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / immunology
  • Multipotent Stem Cells / transplantation*
  • Skin Transplantation / immunology*
  • Transplantation Conditioning / methods
  • Transplantation Tolerance / immunology*
  • Transplantation, Homologous