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タイトル: | Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy: A Rat Model |
著者: | Yanai, Goichi Hayashi, Takashi Zhi, Qi Yang, Kai-Chiang Shirouzu, Yasumasa Shimabukuro, Takashi Hiura, Akihito Inoue, Kazutomo Sumi, Shoichiro ![]() |
著者名の別形: | 角, 昭一郎 |
発行日: | 28-May-2013 |
出版者: | Public Library of Science |
誌名: | PLoS ONE |
巻: | 8 |
号: | 5 |
論文番号: | e64499 |
抄録: | Islet transplantation is a minimally invasive treatment for severe diabetes. However, it often requires multiple donors to accomplish insulin-independence and the long-term results are not yet satisfying. Therefore, novel ways to overcome these problems have been explored. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs) are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types, promote angiogenesis and modulate inflammation, thereby studied as an enhancer of islet function and engraftment. Electrofusion is an efficient method of cell fusion and nuclear reprogramming occurs in hybrid cells between different cell types. Therefore, we hypothesized that electrofusion between MSC and islet cells may yield robust islet cells for diabetes therapy. We establish a method of electrofusion between dispersed islet cells and MSCs in rats. The fusion cells maintained glucose-responsive insulin release for 20 days in vitro. Renal subcapsular transplantation of fusion cells prepared from suboptimal islet mass (1, 000 islets) that did not correct hyperglycemia even if co-transplanted with MSCs, caused slow but consistent lowering of blood glucose with significant weight gain within the observation period in streptozotocin-induced diabetic rats. In the fusion cells between rat islet cells and mouse MSCs, RT-PCR showed new expression of both rat MSC-related genes and mouse β-cell-related genes, indicating bidirectional reprogramming of both β-cell and MSCs nuclei. Moreover, decreased caspase3 expression and new expression of Ki-67 in the islet cell nuclei suggested alleviated apoptosis and gain of proliferative capability, respectively. These results show that electrofusion between MSCs and islet cells yield special cells with β-cell function and robustness of MSCs and seems feasible for novel therapeutic strategy for diabetes mellitus. |
記述: | 膵島細胞と間葉系幹細胞の融合細胞を用いた糖尿病治療実験に成功 -新しい重症糖尿病治療法の開発に期待-. 京都大学プレスリリース. 2013-05-29. |
著作権等: | © 2013 Yanai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
URI: | http://hdl.handle.net/2433/174251 |
DOI(出版社版): | 10.1371/journal.pone.0064499 |
PubMed ID: | 23724055 |
関連リンク: | http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2013/130529_1.htm |
出現コレクション: | 学術雑誌掲載論文等 |
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