In vitro differentiation of mesenchymal stem cells from dental and oral tissues into Islet-like cell cluster

Abstract

Diabetes mellitus is a complicated metabolic disorder resulting in hyperglycemia and long-term complications e.g. diabetic encephalopathy and neuropathy. Treatments of diabetes and its complications have faced many obstacles. Trend of stem cells (SCs)-based therapy has been proposed as a novel approach. Though, the study using dental SCs in this regard is yet lacking. In this study, human dental pulp SCs (hDPSCs) and human periodontal ligament SCs (hPDLSCs) were employed. The results illustrated the capability of differentiation toward islet-like cells (ILCs) cluster / insulin-producing cells (IPCs) by hDPSCs and hPDLSCs. In addition, higher capacity of differentiation toward ILCs cluster / IPCs by hDPSCs was apparently showed in respects of colony number, gene and protein marker expression. In addition, the hDPSCs-derived ILCs cluster / IPCs released C-PEPTIDE upon glucose stimulation in dose-dependent manner. After induction, Notch target genes, HES-1 and HEY-1, were upregulated. Notch inhibition during each step or throughout the induction protocol resulted in variation of ILCs cluster / IPCs morphology, mRNA and protein marker expression, and functional property. Thus, the results suggested the capability of dental SCs in differentiation toward ILCs cluster / IPCs which might be implied to the possibility of dental SCs used in diabetes treatment. In addition, Notch signaling might participate in the regulation of dental SCs differentiation toward ILCs cluster / IPCs.