Promoting β-cells function by the recapitulation of in vivo microenvironmental differentiation signals.

Abstract

The study aims to transdifferentiate rat bone marrow-derived mesenchymal stem cells (BM-MSCs) more efficiently into islet-like cells and encapsulate and transplant them with vital properties like stability, proliferation, and metabolic activity enhanced for the treatment of T1DM. Trans-differentiation of BM-MCs into islet-like cells induced by high glucose concentration combined with Nicotinamide, ꞵ-Mercaptoethanol, ꞵ-Cellulin, and IGF-1. Glucose challenge assays and gene expression profiles were used to determine functionality. Microencapsulation was performed using the vibrating nozzle encapsulator droplet method with a 1% alginate concentration. Encapsulated ꞵ-cells were cultured in a fluidized-bed bioreactor with 1850 μL/min fluid flow rates and a superficial velocity of 1.15cm/min. The procedure was followed by transplanting transdifferentiated cells into the omentum of streptozotocin (STZ)-induced diabetic Wistar rats. Changes in weight, glucose, insulin, and C-peptide levels were monitored for 2months after transplantation. PDX1, INS, GCG, NKx2.2, NKx6.1, and GLUT2 expression levels revealed the specificity of generated β-cells with higher viability (about 20%) and glucose sensitivity about twofold more. The encapsulated β-cells decreased the glucose levels in STZ-induced rats significantly (P < 0.05) 1week after transplantation. Also, the weight and levels of insulin and C-peptide reached the control group. In contrast to the treated, the sham group displayed a consistent decline in weight and died when loss reached > 20% at day ~ 55. The coated cells secrete significantly higher amounts of insulin in response to glucose concentration changes. Enhanced viability and functionality of β-cells can be achieved through differentiation and culturing, a promising approach toward insulin therapy alternatives.