Establishment of transplantation platform for delivering mouse induced pluripotent stem cell-derived insulin-producing cells (mips-ipcs) for diabetes treatment

Abstract

Pancreatic beta-cell replacement is recognized for feasible type 1 diabetes (T1D) treatment. However, in post-transplantation, the autoimmune destruction incidentally attacks the activity and survival of beta-cells are reported in animal and human. To address these concerns, the generation of immortalized, biocompatible beta-cells, and the engraftment platform are insightfully investigated. The stepwise chemical process was used for in vitro Insulin-producing cells (IPCs) production from mouse gingival fibroblast-induced pluripotent stem cells (mGF-iPSCs). The real-time qRT-PCR, glucose stimulation C-peptide/Insulin secretion, immunostaining, and visible cell methods were examined during IPC differentiation. The encapsulated-IPC beads were loaded into subcutaneous pocket space via transplantation platform. Completed blood count, blood chemistry, C-peptide, HOMA indexes, intraperitoneal glucose tolerance test, and histopathology were analyzed at pre-, post-transplantation and at termination. The 40 cytokines were explored via antibody array detection. In this study, in vitro IPC differentiation protocol wasperceptively dissection. IPC encapsulation achieved to the transplantable capacity.In mice, the catheter insertion and 10% Pluronic-F127 carrying-VEGF-165 (VP) created the subcutaneous pocket formation (SPF), and stimulated angiogenesis and neovascularization surrounding the SPF. Especially, IPC-bead engraftment alleviated hyperglycemia in STZ-induced-diabetic mice-VP + IPC-bead transplantation. In post-transplantation, IPC-bead transplantation showed noimmune response, as well as, IPC-bead maintained the health condition in diabetic mice. The obtained results can be applied as a clinical transplantation protocol for T1D treatment using cell-based therapy.