Improving of transdifferentiation, function and survival rate in microencapsulated ꞵ-cell: in-vitro and in-vivo study
Improving of transdifferentiation, function and survival rate in microencapsulated ꞵ-cell: in-vitro and in-vivo study
Davood Zaeifi,1,*Mahnaz Azarnia,2
1. Biology department, Faculty of Biological Sciences, Tehran North Branch of Islamic Azad University 2. Biology department, Faculty of Biological Sciences, Tehran North Branch of Islamic Azad University
Introduction: The objective of the study is to efficiently transdifferentiate rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into islet-like cells, and encapsulate and transplant them while maintaining vital properties like stability, cell proliferation, and metabolic activity for the treatment of T1DM.
Methods: 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 beta-cells that had been cultured in a fluidized-bed bioreactor to measure their metabolic activity and viability were then transplanted into the omentum of STZ-induced diabetic Wistar rats, and their blood sugar and weight were monitored for two months.
Results: Based on the induction protocol, PDX1, INS, GCG, NKx2.2, NKx6.1, and GLUT2 expression profiles revealed the specificity of generated pancreatic islet cells. Post-islet-like cell transplantation reduced the glucose levels of the streptozotocin (STZ)-induced rats significantly (P< 0.05). In contrast to treated, STZ-induced rats who did not receive encapsulated islets displayed a consistent decline in weight and died when loss reached >20 percent at day ~55.
Conclusion: Enhancing the conditions and means of differentiation and protection of encapsulated cells, particularly for pancreatic beta cells with a limited supply, may be a promising approach for safe cell therapy.