Construction of functional pancreatic artificial islet tissue composed of fibroblast-modified polylactic-co-glycolic acid membrane and pancreatic stem cells

Abstract

Objective To improve the biocompatibility between polylactic- co-glycolic acid membrane and pancreatic stem cells, rat fibroblasts were used to modify the polylactic- co-glycolic acid membrane. Meanwhile, we constructed artificial islet tissue by compound culturing the pancreatic stem cells and the fibroblast-modified polylactic- co-glycolic acid membrane and explored the function of artificial islets in diabetic nude mice. Methods Pancreatic stem cells were cultured on the fibroblast-modified polylactic- co-glycolic acid membrane in dulbecco's modified eagle medium containing activin-A, β-catenin, and exendin-4. The differentiated pancreatic stem cells combined with modified polylactic- co-glycolic acid membrane were implanted subcutaneously in diabetic nude mice. The function of artificial islet tissue was explored by detecting blood levels of glucose and insulin in diabetic nude mice. Moreover, the proliferation and differentiation of pancreatic stem cells on modified polylactic- co-glycolic acid membrane as well as the changes on the tissue structure of artificial islets were investigated by immunofluorescence and haematoxylin and eosin staining. Results The pancreatic stem cells differentiated into islet-like cells and secreted insulin when cultured on fibroblast-modified polylactic- co-glycolic acid membrane. Furthermore, when the artificial islet tissues were implanted into diabetic nude mice, the pancreatic stem cells combined with polylactic- co-glycolic acid membrane modified by fibroblasts proliferated, differentiated, and secreted insulin to reduce blood glucose levels in diabetic nude mice. Conclusion Pancreatic stem cells can be induced to differentiate into islet-like cells in vitro. In vivo, the artificial islet tissue can effectively regulate the blood glucose level in nude mice within a short period. However, as time increased, the structure of the artificial islets was destroyed due to the erosion of blood cells that resulted in the gradual loss of artificial islet function.

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“…Our studies demonstrated that the fibroblasts and the ECM secreted by fibroblast scan effectively improve the biocompatibility of PLGA membrane and pancreatic stem cells, and promote the affinity between pancreatic stem cells and the PLGA membrane scaffold [15]. The pancreatic stem cells grown on the fibroblast-modified PLGA membrane can be induced to differentiate into insulin secreting cells by the two-step induction method, the PLGA artificial islet tissue containing ECM of fibroblasts and insulin secreting cells can secrete insulin and reduce blood glucose within a short term in diabetic nude mice [15]. Fibroblast-modified PLGA membrane plays a mechanical support role in the process of artificial islet tissue formation; however, non-specific inflammatory response is the main cause in primary non-function of islet transplantation [15].…”

“…The pancreatic stem cells grown on the fibroblast-modified PLGA membrane can be induced to differentiate into insulin secreting cells by the two-step induction method, the PLGA artificial islet tissue containing ECM of fibroblasts and insulin secreting cells can secrete insulin and reduce blood glucose within a short term in diabetic nude mice [15]. Fibroblast-modified PLGA membrane plays a mechanical support role in the process of artificial islet tissue formation; however, non-specific inflammatory response is the main cause in primary non-function of islet transplantation [15]. Hence, the research on artificial islet tissue derived from non-antigenic autologous stem cells will have a profound effect on the treatment of diabetes.…”

“…Time to euglycemia and response to glucose challenge were both significantly faster for collagen IV coated scaffolds compared with scaffolds coated with fibronectin, laminin or non-coated control scaffolds treated with serum containing media [14]. In our previous study, we used fibroblasts to modify the PLGA scaffolds, the ECM secreted by fibroblasts, which contains all of these proteins, effectively improve the histocompatibility and cell compatibility of the PLGA membrane, promoted the proliferation and differentiation of pancreatic stem cells [15].…”

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,…”

Polymeric Scaffolds for Pancreatic Tissue Engineering: A Review

“…The modified PLGA membrane showed higher compatibility, improved proliferation, and increased viability of pancreatic stem cells compared with the unmodified membrane. Also, it had an enhanced histocompatibility with nude mice [112].…”