Pancreatic Extracellular Matrix/Alginate Hydrogels Provide a Supportive Microenvironment for Insulin-Producing Cells

Type 1 diabetes mellitus (T1DM), as an autoimmune deficiency disease, is associated with an absolute deficiency of insulin subject to islet beta-cell destruction. Insulin-producing cells (IPCs) differentiated from induced pluripotent stem cells are an ideal replacement origin of beta-cells, which can be applied for cell transplantation therapies in T1DM. At present, more strategies focus on inducing and differentiating to obtain IPCs; however, the unsatisfactory differentiation efficiency and the lack of ideal carriers for in vivo transplantation limited their application. It is necessary to consider the cell microenvironment by constructing a biomimetic niche to improve the differentiation and transplantation efficiency. The main components of the extracellular matrix derived from pancreatic (the niche of beta-cells) decellularization were retained, which could provide the ideal extracellular microenvironment for IPCs. In this research, a hydrogel prepared with alginate (Alg) and the pancreatic extracellular matrix (pECM) was assessed for the beneficial outcomes on encapsulated IPCs. The results showed that pECM/Alg improved the differentiation efficiency and promoted insulin secretion and the expression of insulin-related genes as well. Besides, pECM/Alg-encapsulated IPCs exhibited obvious biocompatibility in vivo, which can prolong the transplantation effect and hypoglycemic function by reducing the inflammatory reaction. RNA-seq indicated that the PI3K/Akt pathway may be related to the improvement of the differentiation efficiency and function of IPCs. In general, the pECM/Alg hydrogel provides an ideal biomimetic microenvironment for IPCs and is suitable for in vivo transplantation.