Influence of metabolically compromised Adipose derived stem cell secretome on islet differentiation and functionality

Abstract

Islet integrity plays a major role in maintaining glucose homeostasis and thus replenishment of damaged islets by differentiation of resident endocrine progenitors into neo islets regulates the islet functionality. Islet differentiation is affected by many factors including crosstalk with various organs by secretome. Adipose derived stem cells (ADSC) secrete a large array of factors in the extracellular milieu that exhibit regulatory effects on other tissues including pancreatic islets. The microenvironment of metabolically compromised human ADSCs (hADSCs) has a detrimental impact on islet functionality. In the present study, the role of secretome was studied on the differentiation of islets. Expression of key transcription factors like HNF–3B, NGN-3, NeuroD, PDX- 1, Maf-A, and GLUT-2 involved in development were differentially regulated in obese hADSC secretome as compared to control hADSC secretome. Islet like cell clusters (ILCCs) functionality and viability were critically hampered under obese hADSC secretome with compromised yield, morphometry, lower expression of C-peptide and Glucagon as well as higher ROS activity and cell death parameters. This study provides considerable insights on two major findings which are (i) exploring the use of hADSC secretome in islet differentiation and (ii) understanding the regulating effect of altered hADSC secretome under a metabolically compromised condition.