Introduction and Objective: Obesity associated with type 2 diabetes (T2DM) is known to cause white adipose tissue hyperplasia associated with oxidative stress. Stem/ progenitor cell therapy may provide a novel strategy for treating obesity- and diabetes-related complications. Our laboratory has shown success in using p53-silenced endothelial progenitor cells (EPCs) in disease models such as hyperglycemia-associated peripheral vascular disease (PVD) and Kidney Disease. Subsequently we have shown conditioned media derived from p53shMSCs reduced apoptosis and helped to improve endothelial health via antioxidant gene upregulation in hyperglycemia. So we decided to investigate whether exosomes derived from P53sh-MSCs conditioned media (CM) can be a therapeutic cell free option to help reduce oxidative stress and inhibit adipogenesis in T2DM/obesity states.Methods: Ad-human-P53 (TP53)-shRNA is used to silence P53, and Ad-scrambled-null-shRNA was used as control in BM-MSCs. Exosomes were isolated from the condition medium(CM) collected from BM-MSCs transduced with either Ad-P53HS or scrambled (three variables) as described in our previous publications. In vitro, adipose MSCs (made adipogenic with responsive adipogenic media) were exposed to exosomes derived from p53-sh-BM-MSC-CM. The adipo-MSCs were analyzed by Oil O red stain. Area of Oil red stain was calculated by ImageJ analysis, followed by fat-specific gene expression qPCRResults: Adipogenesis was noted and stained by Oil red O staining of lipid droplets. Decrease in oil droplets was noted in cells exposed to exosomes derived from P53sh-MSCs CM as compared to exosomes derived from scrambled CM by nearly 50%.. Currently we are conducting qPCR for adipogenic genes however prelim results indicate an upregulation of antioxidant pathway in the treated groupConclusion: Exosomes from P53sh-MSCs-CM reduced adipogenesis and can serve as a therapeutic modality to treat obesity and possible complications like non-alcoholic fatty liver disease.
S. Sen: None.
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