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...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/5045 |
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| author | Istvan Kovanecz Robert Gelfand Sheila Sharifzad Alec Ohanian William Brent DeCastro Carley Cooper Guiting Lin Tom Lue Nestor F. Gonzalez-Cadavid |
| author_facet | Istvan Kovanecz Robert Gelfand Sheila Sharifzad Alec Ohanian William Brent DeCastro Carley Cooper Guiting Lin Tom Lue Nestor F. Gonzalez-Cadavid |
| author_sort | Istvan Kovanecz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:25:45Z |
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| id | doaj.art-5e7785fbfefb480b9e48042b46e5f5de |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:25:45Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5e7785fbfefb480b9e48042b46e5f5de2023-11-20T07:03:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114504510.3390/ijms21145045Evaluation 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 IncontinenceIstvan Kovanecz0Robert Gelfand1Sheila Sharifzad2Alec Ohanian3William Brent DeCastro4Carley Cooper5Guiting Lin6Tom Lue7Nestor F. Gonzalez-Cadavid8Division of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADivision of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADivision of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADivision of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADivision of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADivision of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USADepartment of Urology, UCSF School of Medicine, San Francisco, CA 94143, USADepartment of Urology, UCSF School of Medicine, San Francisco, CA 94143, USADivision of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USAHuman 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.https://www.mdpi.com/1422-0067/21/14/5045stem cell damagemuscle-derived stem cellsdyslipidemiacholesterolpalmitic acidfree fatty acids |
| spellingShingle | Istvan Kovanecz Robert Gelfand Sheila Sharifzad Alec Ohanian William Brent DeCastro Carley Cooper Guiting Lin Tom Lue Nestor F. Gonzalez-Cadavid 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 International Journal of Molecular Sciences stem cell damage muscle-derived stem cells dyslipidemia cholesterol palmitic acid free fatty acids |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | stem cell damage muscle-derived stem cells dyslipidemia cholesterol palmitic acid free fatty acids |
| url | https://www.mdpi.com/1422-0067/21/14/5045 |
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