Indirect co‐culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells

Abstract

Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM-MSCS with angiomiR-126 and -210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN).AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrowmesenchymal stem cells (BM-MSCs), followed by 3-day indirect co-culturing with islets laden in collagen (Col)-based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN-containing scaffolds, particularly in the miRNA-126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM-MSCs/miRNA-126 treated group. VEGF was upregulated in the LMN-containing scaffolds in both miRNA-treated groups, specifically in the miRNA-210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN-free scaffolds; while a drastic downregulation was seen in the LMN-containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/Col LMN+ group with miRNA-126. LMNcontaining biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status.bone marrow mesenchymal stem cells, collagen, laminin, miRNA, pancreatic islet | INTRODUCTIONDiabetes is an autoimmune disease in which the pancreatic islet cells fail to make enough insulin. 1 Allogenic and autogenic pancreatic islet cell transplantation is one therapy option for this condition. However, more than 60% of cells are lost in this method due to various causes such as inflammatory reactions. 2,3 Moreover, Extra Cellular Matrix (ECM) is disrupted and interstitial vascular connections are broken upon the isolation of the islets by enzymatic digestion, resulting in a significant loss in cell survival. 4,5 In this context, strategies to repair