A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo

Abstract

It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets. In vitro, islet function was measured by a glucose-stimulated insulin secretion test; cytokines in cultured supernatants were assessed by enzyme-linked immunosorbent assay; and gene expression was analyzed by reverse transcription-quantitative PCR. In vivo, islet transplantation was performed in rats, and graft function and survival were monitored by measuring the blood glucose levels. In vitro, the SIS-MSC scaffold was associated with improved islet viability and enhanced insulin secretion compared with the controls, as well as with the increased the expression of insulin 1 (Ins1), pancreatic and duodenal homeobox 1 (Pdx1), platelet endothelial cell adhesion molecule 1 [Pecam1; also known as cluster of differentiation 31 (CD31)] and vascular endothelial growth factor A (Vegfa) in the islets, increased growth factor secretion, and decreased tumor necrosis factor (TNF) secretion. In vivo, the SIS-MSC scaffold was associated with improved islet function and graft survival compared with the SIS and control groups. On the whole, our findings demonstrate that the SIS-MSC scaffold significantly improved pancreatic islet function and survival in vitro and in vivo. This improvement may be associated with the upregulation of insulin expression, the improvement of islet microcirculation and the secretion of cytokines.

Multipotent mesenchymal stromal cells enhance insulin secretion from human islets via N-cadherin interaction and prolong function of transplanted encapsulated islets in mice

“…This observation is supported by findings in rodents, where the contact between MSC and rat islets maintained and increased glucose-induced insulin secretion [ 35 , 36 ]. Rat islets manifested improved viability when cocultured with MSC at days 7 and 14 [ 37 ]; however, in our experimental in vitro conditions, where we performed insulin secretion assays after 3 days of coculture, islet viability was not influenced since total insulin amounts, obtained by extraction with acid ethanol, were comparable in all conditions. Based on the potentiating effect of MSC on insulin secretion, we assessed the direct cell–cell contact between human islet cells and MSC in pseudoislet formation.…”

Transplantation sites for human and murine islets

“…However, Kim et al reported that transplantation into the omental pouch produced a higher mortality rate and required a longer operative time, so we did not assess it in the present study. Epididymal fat pad and intestinal submucosa in large animals have been investigated for encapsulated islets with good success rates [ 45 , 46 ].…”

The emerging field of pancreatic tissue engineering: A systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells

“…Scaffold size, mechanical stability, and diffusion distances affect the choice further. Among the in vivo studies included (n = 91) the ISC/scaffold construct was transplanted into subcutaneous locations (n = 31), 27,51,69,92–94,112,115,120,133,135,145,147,156,157,171,212–225 the peritoneal cavity (n = 19), 18,26,56,63,65–68,101,134,135,173,195,226–232 an omental pouch (n = 14), 57,59,81,118,119,163,174,225,233–238 the renal capsule (n = 18), 54,…”