並列タイトル等膵全摘糖尿病ブタに対する細胞工学を利用した膵島/脂肪由来間葉系幹細胞複合シート皮下移植の検討
授与機関名Nagasaki University (長崎大学)
一般注記Introduction: Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs.Methods: Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n ¼ 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretionwas measured by insulin stimulation index.Results: Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed.Conclusions: Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1302号 学位授与年月日:令和3年3月3日
Author: Mampei Yamashita, Toshiyuki Adachi, Tomohiko Adachi, Shinichiro Ono, Naomi Matsumura, Kyoichiro Maekawa, Yusuke Sakai, Masaaki Hidaka, Kengo Kanetaka, Tamotsu Kuroki, Susumu Eguchi
Citation: Regenerative Therapy, 16, pp.42-52 ; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-03-03)
一次資料へのリンクURLhttps://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=26551&item_no=1&attribute_id=70&file_no=1 （fulltext）
著作権情報Copyright © 2021, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).
関連情報http://hdl.handle.net/10069/40571
関連情報（DOI）10.1016/j.reth.2020.12.005
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）