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
Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performed<br />with stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.<br />We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stem<br...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/14/5045 |
| Summary: | Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performed<br />with stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.<br />We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stem<br />cells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunction<br />was impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures<br />(GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemic<br />serum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatin<br />overexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) from<br />the T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O lean<br />female rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate as<br />lipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the female<br />dyslipidemic serum was found, but diering between both lipid factors, so that each one appears to<br />contribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/O<br />in vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value for<br />MDSC damage. |
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| ISSN: | 1661-6596 1422-0067 |