Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy

• Material Type: 博士論文
• Title: Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy
• Author/Editor: 山下, 万平
• Author Heading: 山下, 万平
• Publication, Distribution, etc.: Elsevier B.V.
• Publication Date: 2021-03-03
• Publication Date (W3CDTF): 2021-03-03
• Alternative Title: 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
• Periodical title: Regenerative Therapy
• No. or year of volume/issue: 16
• Volume: 16
• Pages: 42-52
• ISSN (Periodical Title): ISSN : 2352-3204
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2021-03-03
• Dissertation Number: 甲医歯薬第1302号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: Islet transplantation; Adipose-derived mesenchymal stem cells; Subcutaneous; Pig; Type 1 diabetes mellitus
• Target Audience: 一般
• Note (General): 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)
• Source: https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=26551&item_no=1&attribute_id=70&file_no=1 （fulltext）; https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=26551&item_no=1&attribute_id=70&file_no=1
• Access Restrictions: インターネット公開
• Rights (production): 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/).
• Related Material: http://hdl.handle.net/10069/40571
• Related Material (DOI): 10.1016/j.reth.2020.12.005
• Data Provider (Database): 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）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ