Abstract
Islet cell transplantation is considered an ideal treatment for insulin-deficient diabetes, but implantation sites are limited and show low graft survival. Cell sheet technology and adipose-derived stem cells (ADSCs) can be useful tools for improving islet cell transplantation outcomes since both can increase implantation efficacy and graft survival. Herein, the optimal transplantation site in diabetic mice was investigated using islets and stem cell sheets. We constructed multi-layered cell sheets using rat/human islets and human ADSCs. Cell sheets were fabricated using temperature-responsive culture dishes. Islet/ADSC sheet (AI sheet) group showed higher viability and glucose-stimulated insulin secretion than islet-only group. Compared to islet transplantation alone, subcutaneous AI sheet transplantation showed better blood glucose control and CD31+ vascular traits. Because of the adhesive properties of cell sheets, AI sheets were easily applied on liver and peritoneal surfaces. Liver or peritoneal surface grafts showed better glucose control, weight gain, and intraperitoneal glucose tolerance test (IPGTT) profiles than subcutaneous site grafts using both rat and human islets. Stem cell sheets increased the therapeutic efficacy of islets in vivo because mesenchymal stem cells enhance islet function and induce neovascularization around transplanted islets. The liver and peritoneal surface can be used more effectively than the subcutaneous site in future clinical applications.
Highlights
Diabetes mellitus occurs because of the loss or impaired function of insulin-secreting pancreatic beta cells
On day 1, both islet and islet/sheet groups showed similar response after culture. These results indicate that adipose-derived stem cells (ADSCs) can play a cytoprotective role in islet cell glucose-sensitive responses, but the islet-only group exhibited significantly decreased glucose response survival after culture or transplantation, and AI sheets can be implemented as effective tools for after culture
These results indicate that ADSCs can play a cytoprotective role in islet cell survival after transplantation
Summary
Diabetes mellitus occurs because of the loss or impaired function of insulin-secreting pancreatic beta cells. Type 1 diabetes (T1D) is characterized by beta cell destruction due to autoimmune defects. Compared to conventional insulin injections, recent therapeutic approaches aim to restore endogenous. Islet transplantation is the cell therapy option in practice for T1D management, with the potential to restore normal blood glucose regulation. Islet culture offers several advantages, including ensuring the quality of islet preparations [1] to possibly decreasing allograft tissue immunogenicity [2]. This approach is limited by requiring an adequate functional islet number to achieve normal glycemic levels. The loss of functional islet mass has been associated with stable islet engraftment [3]
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