Related Experiment Video
Updated: May 10, 2026
A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model
Goichi Yanai1, Takashi Hayashi, Qi Zhi
1Department of Organ Reconstruction, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
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.
Insights
Electrofusion of islet cells and mesenchymal stem cells (MSCs) created hybrid cells that improved blood glucose in diabetic rats. This novel cell therapy shows promise for treating diabetes mellitus.
Area of Science:
- Regenerative Medicine
- Cell Therapy
- Diabetes Research
Background:
- Islet transplantation for diabetes is limited by donor availability and long-term efficacy.
- Isolated islets are fragile, prone to apoptosis, and have poor proliferative capacity.
- Mesenchymal stem cells (MSCs) offer proliferative, anti-apoptotic, and immunomodulatory benefits.
Purpose of the Study:
- To investigate the potential of electrofusion between islet cells and MSCs for enhanced diabetes therapy.
- To evaluate the characteristics and therapeutic efficacy of the resulting hybrid cells.
Main Methods:
- Developed an electrofusion method for rat islet cells and MSCs.
- Assessed glucose-responsive insulin release in vitro.
- Transplanted fusion cells into streptozotocin-induced diabetic rats.
- Analyzed gene expression and apoptosis/proliferation markers via RT-PCR and caspase3/Ki-67 staining.
Main Results:
- Fusion cells exhibited glucose-responsive insulin release in vitro for 20 days.
- Transplantation of suboptimal islet mass (1,000 islets) fused with MSCs led to consistent blood glucose reduction and weight gain in diabetic rats.
- Bidirectional gene reprogramming was observed in rat-mouse hybrid cells.
- Reduced apoptosis (caspase3) and increased proliferation (Ki-67) were noted in islet cell nuclei.
Conclusions:
- Electrofusion between MSCs and islet cells generates robust hybrid cells with both β-cell function and MSC resilience.
- This approach represents a feasible novel therapeutic strategy for diabetes mellitus.
