Watanabe Hironosuke, Tsuchiya Tomoshi, Shimoyama Koichiro, Shimizu Akira, Akita Sadanori, Yukawa Hiroshi, Baba Yoshinobu, Nagayasu Takeshi
Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Division of Surgical Oncology, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Translational Research Center, Research Institute for Science & Technology, Tokyo University of Science, Chiba, Japan.
J Surg Res. 2018 Jul;227:17-27. doi: 10.1016/j.jss.2018.01.016. Epub 2018 Mar 2.
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.
肺移植后的免疫抑制是移植物存活的关键因素。然而，免疫抑制方案所引发的众所周知的并发症为研究减少这些药物使用的方法提供了契机。最近，关于脂肪组织来源的间充质干细胞（ADMSC）通过分泌肝细胞生长因子产生的免疫调节作用有了一项有前景的发现。为了减轻标准免疫抑制方案的不良反应，我们的研究旨在利用大鼠肺移植模型研究ADMSC对免疫反应的影响。
在原位左肺移植后立即经静脉给予每只大鼠自身的ADMSC。实验对象分为四组：1）对照组（C组）移植后不进行处理；2）ADMSC组（A组）移植后经静脉单次注射ADMSC；3）他克莫司组（T组）移植后每24小时给予他克莫司（0.5mg/kg）；4）ADMSC与他克莫司组（AT组）移植后每24小时经静脉单次注射ADMSC并联合给予他克莫司。
AT组经组织学证实的排斥分级显著低于T组。AT组血清肝细胞生长因子水平及cMet表达伴低CD40表达也显著高于T组肺移植物。
这些结果表明，ADMSC与他克莫司联合应用是肺移植中一种有益的治疗方法。
