並列タイトル等ドナーおよびレシピエント脂肪由来の間葉系幹細胞療法を用いたラット肺移植
授与機関名Nagasaki University (長崎大学)
一般注記Background: Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model.Methods: Subjects were divided into no treatment, tacrolimus administration, recipient ADMSC administration, donor ADMSC administration, and mixed donor and recipient ADMSC administration groups. ADMSC-administered groups were also treated with tacrolimus. Histologic study, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction were used for various analyses.Results: Fluorescently labeled ADMSCs were predominant in the grafted donor lung, but not in the recipient lung, on day 5. On day 7, the pathologic rejection grades of the grafted donor lung were significantly lower in the ADMSC-administered groups (P < .05) and did not differ among these groups. Although serum hepatocyte growth factor and vascular endothelial growth factor levels did not differ among the groups, interleukin 10 level was slightly higher in the ADMSC-administered groups. The numbers of infiltrating regulatory T cells in the grafted lung were significantly higher in the ADMSC-administered groups (P < .05) but did not differ with cell origin. Transcriptional analysis suggested interleukin 6 suppression to be the main overlapping immunosuppressive mechanism, regardless of origin. Therefore, a donor or recipient origin may not influence the immunosuppressive efficacy of ADMSCs in our rat lung transplantation model.Conclusions: Collectively, the results indicate that allogenic ADMSCs, regardless of their origin, may exert similar immunosuppressive effects in clinical organ transplantation.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1464号 学位授与年月日:令和4年9月7日
Author: Koichiro Shimoyama, Tomoshi Tsuchiya, Hironosuke Watanabe, Abdelmotagaly Ergalad, Mayumi Iwatake, Takuro Miyazaki, Yasumasa Hashimoto, Yu-I. Hsu, Go Hatachi, Keitaro Matsumoto, Mitsutoshi Ishii, Satoshi Mizoguchi, Ryoichiro Doi, Koichi Tomoshige, Tetsuji Yamaoka, and Takeshi Nagayasu
Citation: Transplantation Proceedings, article in press
identifier:Nagasaki University (長崎大学), 博士(医学) (2022-09-07)
http://hdl.handle.net/10069/00041830
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