Adipose-derived mesenchymal stem cells attenuate rejection in a rat lung transplantation model

• Published in: The Journal of surgical research Vol. 227; pp. 17 - 27
• Main Authors: Watanabe, Hironosuke, Tsuchiya, Tomoshi, Shimoyama, Koichiro, Shimizu, Akira, Akita, Sadanori, Yukawa, Hiroshi, Baba, Yoshinobu, Nagayasu, Takeshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018
• Subjects: Adipose tissue–derived mesenchymal stem cell; Hepatocyte growth factor; Lung transplantation; Adipose tissue–derived mesenchymal stem cell; Hepatocyte growth factor; Lung transplantation
• ISSN: 0022-4804; 1095-8673; 1095-8673
• DOI: 10.1016/j.jss.2018.01.016

Immunosuppression following lung transplantation is a key aspect to the graft's survival. However, the well-known complications that are caused by immunosuppressive regimens present an opportunity to study ways to minimize the usage of these drugs. Recently, a promising discovery has been made pertaining to the immunomodulatory effects of adipose tissue–derived mesenchymal stem cells (ADMSCs) through their secretion of hepatocyte growth factor. In the hopes of mitigating the adverse effects of standard immunosuppressive regimens, our study aims to investigate the effects of ADMSCs on the immune response utilizing a rat lung transplantation model. Each rat's own ADMSCs were intravenously administered immediately after orthotopic left lung transplantation. The experimental subjects were divided into four groups: 1) control group (group C) was administered no treatment following transplantation; 2) ADMSC group (group A), administered a single intravenous injection of ADMSCs following transplantation; 3) tacrolimus group (group T), administered tacrolimus (0.5 mg/kg) every 24 h following transplantation; and 4) ADMSC and tacrolimus group (AT group) administered a single intravenous injection of ADMSCs in combination with tacrolimus every 24 h following transplantation. The histologically proven rejection grade in group AT was significantly lower than that in group T. The serum levels of hepatocyte growth factor and the expression of cMet in group AT accompanied by low CD40 expression were also significantly higher than those of the lung grafts of group T. These results suggest that co-administration of ADMSCs with tacrolimus is a beneficial therapeutic approach in lung transplantation.