Bone marrow-derived mesenchymal stem cells inhibit acute rejection of rat liver allografts in association with regulatory T-cell expansion.
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.
Wang
Y
Y
Key Laboratory of Multi-Organ Combined Transplantation, National Ministry of Health, Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Zhang
A
A
Ye
Z
Z
Xie
H
H
Zheng
S
S
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous / Q000473:pathology
D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit