Transforming growth factor-[beta]-Expressing Mesenchymal Stem Cells Induce Local Tolerance in a Rat Liver Transplantation Model of Acute Rejection

Acute rejection is commonly encountered for long-term survival in liver transplant (LT) recipients and may impact their long-term survival if rejection is severe or recurrent. The aim of this study is to examine the therapeutic potential of transforming growth factor (TGF-[beta])-overexpressing mese...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2016-11, Vol.34 (11), p.2681
Main Authors: Tang, Jincao, Yang, Renjie, Lv, Ling, Yao, Aihua, Pu, Liyong, Yin, Aihong, Li, Xiangcheng, Yu, Yue, Nyberg, Scott L, Wang, Xuehao
Format: Article
Language:English
Subjects:
Grafting
Grafts
Growth factors
Immunity
Immunology
Immunosuppression
Liver
Liver transplantation
Liver transplants
Lymphocytes
Mesenchymal stem cells
Rats
Rejection
Rodents
Skin & tissue grafts
Stem cells
Survival
Transfusion
Transplantation
Transplants & implants
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Summary:Acute rejection is commonly encountered for long-term survival in liver transplant (LT) recipients and may impact their long-term survival if rejection is severe or recurrent. The aim of this study is to examine the therapeutic potential of transforming growth factor (TGF-[beta])-overexpressing mesenchymal stem cells (MSCs) in inducing a local immunosuppression in liver grafts after transplantation. MSCs were transduced with a lentiviral vector expressing the human TGF-[beta]1 gene; TGF-[beta]1-overexpressing MSCs (designated as TGF/MSCs) were then transfused into the liver grafts via the portal vein of a rat LT model of acute rejection. Rejection severity was assessed by clinical and histologic analysis. The immunity suppression effects and mechanism of TGF/MSCs were tested, focusing on their ability to induce generation of regulatory T cells (Tregs) in the liver grafts. Our findings demonstrate that transfusion of TGF/MSCs prevented rejection, reduced mortality, and improved survival of rats after LT. The therapeutic effects were associated with the immunosuppressive effects of MSCs and TGF-[beta]1. Their reciprocal effects on Tregs induction and function resulted in more CD4+Foxp3+Helios- induced Tregs, fewer Th17 cells, and improved immunosuppressive effects in local liver grafts. Thus, TGF/MSCs can induce a local immunosuppressive effect in liver grafts after transplantation. The immunomodulatory activity of TGF-[beta]1 modified MSCs may be a gateway to new therapeutic approaches to prevent organ rejection in clinical transplantation. Stem Cells 2016;34:2681-2692
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.2437