Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence

Abstract

Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performed with stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results. We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stem cells (MDSC) were from long-term T2D/O male rats, their repair efficacy for erectile dysfunction was impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures (GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemic serum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatin overexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) from the T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O lean female rats. In the current work we studied the in vitro effects of cholesterol and Na palmitate as lipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the female dyslipidemic serum was found, but differing between both lipid factors, so that each one appears to contribute specifically to the stem cell damaging effects of dyslipidemic serum in vitro and T2D/O in vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value for MDSC damage.