Bone marrow-derived mesenchymal stem cells inhibit acute rejection of rat liver allografts in association with regulatory T-cell expansion

Transplant Proc. 2009 Dec;41(10):4352-6. doi: 10.1016/j.transproceed.2009.08.072.


Bone marrow-derived mesenchymal stem cells (MSCs) exhibit immunosuppressive functions in vitro and in vivo. We investigated the immunoregulatory effects of rat MSCs in a model of allogeneic liver transplantation. Brown Norway rats received livers from inbred Lewis rats, and at designated intervals, infusions of MSCs derived from recipient, donor, or third-party rats. Allograft rejection and recipient survival rates were recorded. In particular, changes in circulating regulatory T cells (Tregs) were measured. After administration of MSCs derived from each of the 3 strains, allograft recipients demonstrated markedly longer survival compared with control animals. Histologic analysis revealed significant inhibition of allograft rejection. The MSCs induced generation of CD4+CD25+Foxp3+ Tregs. We concluded that MSCs inhibit acute rejection of allografts after liver transplantation, and propose that the immunoregulatory effects of MSCs are associated with expansion of Tregs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Culture Techniques
  • Graft Rejection / prevention & control*
  • Graft Survival
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Liver Transplantation / immunology*
  • Liver Transplantation / pathology
  • Liver Transplantation / physiology*
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Models, Animal
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Rats, Wistar
  • T-Lymphocytes, Regulatory / immunology*
  • Transplantation, Homologous / pathology


  • CD4 Antigens
  • Interleukin-2 Receptor alpha Subunit