Adipose-derived mesenchymal stem cells suppress of acute rejection in small bowel transplantation
Yu Zhang1, Qinghong Meng2, Yanyan Zhang3, Xiaobo Chen4, Yuliang Wang5
1 Department of Anesthesia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China
2 Department of Clinical Laboratory Medicine, Sino-Singapore Eco-City Hospital of Tianjin Medical University, Tianjin, People's Republic of China
3 Institut National de la Santé et de la Recherche Médicale (INSERM), Micronit; Institut Gustave Roussy, Univ Paris-Sud, Université Paris Saclay, Villejuif, France
4 Union Stem and Gene Engineering Co., Ltd, Tianjin, People's Republic of China
5 Department of Clinical Laboratory Medicine, 2nd Hospital of Tianjin Medical University, Tianjin Institute of Urology; Tianjin First Central Hospital, Tianjin, People's Republic of China
Department of Clinical Laboratory Medicine, 2nd Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin
People's Republic of China
Source of Support: None, Conflict of Interest: None
Background/Aims: Adipose-derived mesenchymal stem cells (ADSCs) possess immunosuppressive activity and hold promise in autologous cell-based therapies. The aim of this study was to determine whether autologous ADSCs can improve outcomes in the rat small bowel transplantation (SBT) model.
Materials and Methods: Allogeneic SBT followed by implantation of autologous ADSCs through the penile vein was conducted in Brown-Norway (BN) donor rats with Lewis (LEW) recipient rats infused with phosphate buffered solution as the control. Allograft and recipient peripheral blood were obtained. We assessed histopathology, apoptosis, cytokines, and regulatory T cells (Tregs). One-way analysis of variance was applied to assess the significance of the data.
Results: It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival rate. In addition, there were significantly fewer apoptotic cells in allograft mucosae in the ADSC group in comparison with the control group. Furthermore, levels of interleukin (IL)-10 and transforming growth factor-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that there were significantly more peripheral Tregs after the infusion of ADSCs.
Conclusions: These results demonstrate that implanted autologous ADSCs improve allogeneic small bowel allograft outcomes by attenuating the acute rejection and reducing inflammatory responses.