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Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo

1
Division of Urology, Department of Surgery, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA
2
Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1768, USA
3
Department of Medicine, Charles Drew University of Medicine and Science, Los Angeles, CA 90059, USA
4
Department of Urology, UCSF School of Medicine, San Francisco, CA 94143, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4044; https://doi.org/10.3390/ijms20164044
Received: 22 July 2019 / Revised: 8 August 2019 / Accepted: 10 August 2019 / Published: 19 August 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Autograph stem cell therapy surprisingly has poor efficacy. In the male rat model of T2D/O, it was demonstrated that epigenetic changes, triggered by long-term exposure to the dyslipidemic milieu, led to abnormal global transcriptional signatures (GTS) of genes and microRNAs (miR), and impaired the repair capacity of muscle-derived stem cells (MDSC). This was mimicked in vitro by treatment of MDSC with dyslipidemic serum or lipid factors. The current study aimed to predict whether these changes also occur in stem cells from female 12 weeks old T2D/O rats, a model of FSUI. MDSCs from T2D/O (ZF4-SC) and normal female rats (ZL4-SC) were treated in vitro with either dyslipidemic serum (ZFS) from late T2D/O 24 weeks old female Zucker fatty (ZF) rats, or normal serum (ZLS) from 24 weeks old female Zucker lean (ZL) rats, for 4 days and subjected to assays for fat deposition, apoptosis, scratch closing, myostatin, interleukin-6, and miR-GTS. The dyslipidemic ZFS affected both female stem cells more severely than in the male MDSC, with some gender-specific differences in miR-GTS. The changes in miR-GTS and myostatin/interleukin-6 balance may predict in vivo noxious effects of the T2D/O milieu that might impair autograft stem cell (SC) therapy for FSUI, but this requires future studies. View Full-Text
Keywords: dyslipidemia; muscle-derived stem cells; fat infiltration; apoptosis; wound closure; microRNA; myostatin; interleukin-6 dyslipidemia; muscle-derived stem cells; fat infiltration; apoptosis; wound closure; microRNA; myostatin; interleukin-6
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Kovanecz, I.; Gelfand, R.; Lin, G.; Sharifzad, S.; Ohanian, A.; Ricks, R.; Lue, T.; Gonzalez-Cadavid, N.F. Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo. Int. J. Mol. Sci. 2019, 20, 4044.

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