Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.

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 fragil...

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Autores principales:	Goichi Yanai, Takashi Hayashi, Qi Zhi, Kai-Chiang Yang, Yasumasa Shirouzu, Takashi Shimabukuro, Akihito Hiura, Kazutomo Inoue, Shoichiro Sumi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9120ab3ec79c41cc87e54778fdedc7f3
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spelling	oai:doaj.org-article:9120ab3ec79c41cc87e54778fdedc7f32021-11-18T07:44:07ZElectrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.1932-620310.1371/journal.pone.0064499https://doaj.org/article/9120ab3ec79c41cc87e54778fdedc7f32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23724055/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Islet 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.Goichi YanaiTakashi HayashiQi ZhiKai-Chiang YangYasumasa ShirouzuTakashi ShimabukuroAkihito HiuraKazutomo InoueShoichiro SumiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64499 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Goichi Yanai Takashi Hayashi Qi Zhi Kai-Chiang Yang Yasumasa Shirouzu Takashi Shimabukuro Akihito Hiura Kazutomo Inoue Shoichiro Sumi Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
description	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.
format	article
author	Goichi Yanai Takashi Hayashi Qi Zhi Kai-Chiang Yang Yasumasa Shirouzu Takashi Shimabukuro Akihito Hiura Kazutomo Inoue Shoichiro Sumi
author_facet	Goichi Yanai Takashi Hayashi Qi Zhi Kai-Chiang Yang Yasumasa Shirouzu Takashi Shimabukuro Akihito Hiura Kazutomo Inoue Shoichiro Sumi
author_sort	Goichi Yanai
title	Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
title_short	Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
title_full	Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
title_fullStr	Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
title_full_unstemmed	Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
title_sort	electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9120ab3ec79c41cc87e54778fdedc7f3
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Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.

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