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

Autor: Carley Cooper, Guiting Lin, Robert Gelfand, Nestor F. Gonzalez-Cadavid, Alec Ohanian, William Brent DeCastro, Istvan Kovanecz, Sheila Sharifzad, Tom F. Lue
Rok vydání: 2020
Předmět:
0301 basic medicine
endocrine system diseases
Urinary Incontinence
Stress
medicine.medical_treatment
Palmitic Acid
Type 2 diabetes
Myostatin
wound closure
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
stem cell damage
lcsh:QH301-705.5
Cells
Cultured
Spectroscopy
microRNA
biology
Stem Cells
apoptosis
free fatty acids
General Medicine
Stem-cell therapy
Computer Science Applications
myostatin
030220 oncology & carcinogenesis
fat infiltration
Biomarker (medicine)
Female
Stem cell
medicine.medical_specialty
muscle-derived stem cells
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Internal medicine
medicine
Animals
Obesity
Physical and Theoretical Chemistry
Molecular Biology
business.industry
Cholesterol
dyslipidemia
Organic Chemistry
cholesterol
nutritional and metabolic diseases
medicine.disease
In vitro
Rats
Rats
Zucker
Disease Models
Animal
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
Diabetes Mellitus
Type 2
chemistry
Apoptosis
biology.protein
business
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 14
International Journal of Molecular Sciences, Vol 21, Iss 5045, p 5045 (2020)
ISSN: 1422-0067
Popis: Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performedwith 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 stemcells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunctionwas 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 dyslipidemicserum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatinoverexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) fromthe T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O leanfemale rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate aslipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the femaledyslipidemic serum was found, but diering between both lipid factors, so that each one appears tocontribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/Oin vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value forMDSC damage.
Databáze: OpenAIRE
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