Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy: A Rat Model

Goichi Yanai, Takashi Hayashi, Qi Zhi, Kai Chiang Yang, Yasumasa Shirouzu, Takashi Shimabukuro, Akihito Hiura, Kazutomo Inoue, Shoichiro Sumi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere64499
JournalPLoS One
Volume8
Issue number5
DOIs
Publication statusPublished - May 28 2013

Fingerprint

electrofusion
islets of Langerhans
Medical problems
Cell- and Tissue-Based Therapy
Stem cells
Mesenchymal Stromal Cells
Islets of Langerhans
diabetes
stem cells
Rats
animal models
therapeutics
cell fusion
Cell Fusion
Fusion reactions
cells
rats
cell nucleus
Cell Nucleus
insulin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Yanai, G., Hayashi, T., Zhi, Q., Yang, K. C., Shirouzu, Y., Shimabukuro, T., ... Sumi, S. (2013). Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy: A Rat Model. PLoS One, 8(5), [e64499]. https://doi.org/10.1371/journal.pone.0064499

Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy : A Rat Model. / Yanai, Goichi; Hayashi, Takashi; Zhi, Qi; Yang, Kai Chiang; Shirouzu, Yasumasa; Shimabukuro, Takashi; Hiura, Akihito; Inoue, Kazutomo; Sumi, Shoichiro.

In: PLoS One, Vol. 8, No. 5, e64499, 28.05.2013.

Research output: Contribution to journalArticle

Yanai, G, Hayashi, T, Zhi, Q, Yang, KC, Shirouzu, Y, Shimabukuro, T, Hiura, A, Inoue, K & Sumi, S 2013, 'Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy: A Rat Model', PLoS One, vol. 8, no. 5, e64499. https://doi.org/10.1371/journal.pone.0064499
Yanai, Goichi ; Hayashi, Takashi ; Zhi, Qi ; Yang, Kai Chiang ; Shirouzu, Yasumasa ; Shimabukuro, Takashi ; Hiura, Akihito ; Inoue, Kazutomo ; Sumi, Shoichiro. / Electrofusion of Mesenchymal Stem Cells and Islet Cells for Diabetes Therapy : A Rat Model. In: PLoS One. 2013 ; Vol. 8, No. 5.
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