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亜鉛イオン濃度変化は脂肪由来幹細胞から作成するインスリン産生細胞の成熟を反映する
著者
太田, 昇吾 徳島大学大学院医科学教育部(医学専攻)
Wada, Yuma Tokushima University
キーワード
Insulin producing cell (IPC)
adipose derived stem cell (ADSC)
zinc ion (Zn)
maturation
differentiation
資料タイプ
学位論文
抄録
The generation of insulin-producing cells (IPCs) from pluripotent stem cells could be a breakthrough treatment for type 1 diabetes. However, development of new techniques is needed to exclude immature cells for clinical application. Dithizone staining is used to evaluate IPCs by detecting zinc. We hypothesised that zinc ion (Zn2+) dynamics reflect the IPC maturation status. Human adipose-derived stem cells were differentiated into IPCs by our two-step protocol using two-dimensional (2D) or 3D culture. The stimulation indexes of 2D -and 3D-cultured IPCs on day 21 were 1.21 and 3.64 (P < 0.05), respectively. The 3D-cultured IPCs were stained with dithizone during culture, and its intensity calculated by ImageJ reached the peak on day 17 (P < 0.05). Blood glucose levels of streptozotocin-induced diabetic nude mice were normalised (4/4,100%) after transplantation of 96 3D-cultured IPCs. Zn2+ concentration changes in the medium of 3D cultures had a negative value in the early period and a large positive value in the latter period. This study suggests that Zn2+ dynamics based on our observations and staining of zinc transporters have critical roles in the differentiation of IPCs, and that their measurement might be useful to evaluate IPC maturation as a non-destructive method.
掲載誌名
Scientific Reports
ISSN
20452322
出版者
Springer Nature
9
開始ページ
18731
発行日
2019-12-10
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Shogo Ohtaの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3428号
学位記番号
甲医第1458号
学位授与年月日
2020-06-25
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系