Regeneration of insulin-producing cells from iPS cells using functionalized scaffolds and solid lipid nanoparticles

Abstract

BackgroundFrom ongoing human clinical trials, cell therapy for diabetic treatment using islet-like organoid generation from induced pluripotent stem cells (iPSCs) appears to have a promising future. MethodsDevelopment of islet cells from iPSCs was guided in activin A- and Wnt3a-grafted gelatin-polyacrylamide inverted colloidal crystal scaffolds (activin A-Wnt3a-Gel-PAAM ICCS) with pore sizes of 70 and 160 µm, followed by regulation with fibroblast growth factor 7-grafted retinoic acid-entrapped solid lipid nanoparticles (FGF7-RA-SLNs). Significant FindingsFGF7-RA-SLNs diffused into activin A-Wnt3a-Gel-PAAM ICCS, and controlled differentiation of definitive endoderm (DE) cells into islet cells. The immunochemical staining, flow cytometry and western blot demonstrated combined effects among activin A and Wnt3a, FGF7 and RA in materials for the 2-step differentiation. Wnt3a on the pore surface promoted activin A activity for generating DE cells, and FGF7 enhanced RA activity for producing islet cells. Under glucose stimulation, activin A-Wnt3a-Gel-PAAM ICCS with pore sizes of 70 µm were prone to regenerate insulin-producing β-cells rather than α cells. The optimized conditions for insulin secretion from β-like cells in this study were pore size of 70 µm, Gel:PAAM of 7:3, 100 ng/mL activin A, 100 ng/mL Wnt3a, 50 ng/mL FGF7 and 600 ng/mL RA. Activin A-Wnt3a-Gel-PAAM ICCS associated with FGF7-RA-SLNs can be effective in forming biomimetic pancreas and supporting cell therapy from iPSCs for diabetic management.