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Pre-Culture of Scaffolds with Vasculogenic Cells Improves Stem Cell-Derived β Cell Transplantation
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DOI：10.1177/19373341251398054.png)
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Abstract
En 中文
Transplantation of stem cell-derived beta cells is a promising treatment for type-1 diabetes, increasing the supply of insulin-producing cells beyond that of cadaveric islet transplantation. Transplant success is limited by cell death after transplantation, with insufficient oxygen and nutrient accessibility strongly contributing to apoptosis and de-differentiation. Herein, we investigate cotransplantation of endothelial cells and fibroblasts with stem cell-derived beta cells to enhance survival and function posttransplantation. A microporous poly (lactide coglycolide) scaffold was used for culture and transplantation of stem cell-derived beta cells. Coculture of the stem cell-derived beta cells with endothelial cells and fibroblasts generated vascular networks during in vitro culture, which persisted through transplantation and enhanced in vivo vascularization. 7-days of in vitro culture supported enhanced survival of transplanted cells, though function in terms of insulin secretion and reduction of hyperglycemia was compromised. However, 3-days of preculture led to both improved survival and function of the stem cell-derived beta cells, with transplant recipients demonstrating reduced fasting blood glucose levels. These studies demonstrate the potential and some constraints on the application of vascularization strategies to enhance function of stem cell-derived beta cells with transplantation to extrahepatic sites. Impact Statement Cell death after transplantation due to hypoxia is a significant barrier to cell replacement therapy for type 1 diabetes. While pancreatic islets are highly vascularized, stem cell-derived beta cells lack any vasculature and thus are highly susceptible to dysregulation or cell death upon transplantation. In order to enhance engraftment and thus improve transplanted cell function, stem cell-derived beta cells can be cocultured with vasculogenic cells to form microvascular networks in vitro that persist during transplantation and anastomose with host vasculature.
Keywords:
coculture
type 1 diabetes
stem cell-derived beta cell
vessel
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