86-OR: Self-Organized Insulin-Producing ß-Cells Differentiated from Human Omentum-Derived Stem Cells

Abstract

Human omentum-derived mesenchymal stem cells (hO-MSCs) possess a great potential to differentiate into multiple lineages and have self-renewal capacities, allowing them to be utilized as patient-specific cell-based therapeutics. Although various stem cell-derived insulin-producing β-cells have been proposed for the treatment of diabetes mellitus, developing an efficient method to establish highly functionalized insulin-producing β-cells remains a challenging task. Here, we aimed to develop a novel cell culture platform that could regulate important cell-cell/cell-matrix interactions by introducing a fibroblast growth factor 2 (FGF2)-immobilized matrix that can support cell adhesion, proliferation, and differentiation of hO-MSCs into insulin-producing β-cells. Our initial findings demonstrated that cells cultured on an FGF2-immobilized matrix were able to self-organize into insulin-producing β-cell-like progenitors, as evident from the upregulation of pancreatic β-cell-specific markers such as PDX-1, Insulin, and Glut-2. Furthermore, heparan sulfate proteoglycan, gap junction proteins including Cx36 and Cx43, and cell adhesion molecules such as E-cadherin and Ncam1 were significantly upregulated, leading to cell maturation and insulin secretion in the pancreatic niche environment. These results suggest that our novel platform could promote β-cell differentiation and glucose-stimulated insulin secretion from hO-MSCs by enhancing cell-cell junction proteins such as connexins (Cx36, Cx43), E-cadherin, and N-cam. Such a cell culture platform can offer novel strategies to obtain functional pancreatic β-cells from a patient-specific cell sources, ultimately enabling better treatments for diabetes mellitus. Disclosure Y.Hwang: None. Funding National Research Foundation of Korea (2019R1A5A8083404)