| Authors |
Kovanecz I, Vernet D, Masouminia M, Gelfand R, Loni L, Aboagye J, Tsao J, Rajfer
J, Gonzalez-Cadavid NF
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| Submitted By |
Nestor Gonzalez-Cadavid on 4/28/2016 |
| Status |
Published |
| Journal |
The journal of sexual medicine |
| Year |
2016 |
| Date Published |
5/1/2016 |
| Volume : Pages |
13 : 786 - 97 |
| PubMed Reference |
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| Abstract |
Muscle-derived stem cells (MDSCs) and other SCs implanted into the penile
corpora cavernosa ameliorate erectile dysfunction in type 1 diabetic rat models
by replenishing lost corporal smooth muscle cells (SMCs) and decreasing
fibrosis. However, there are no conclusive data from models of type 2 diabetes
(T2D) and obesity., To determine whether MDSCs from obese Zucker (OZ) rats with
T2D at an early stage of diabetes (early diabetic SCs isolated and cultured in
low-glucose medium [ED-SCs]) counteract corporal veno-occlusive dysfunction and
corporal SMC loss or lipo-fibrosis when implanted in OZ rats at a late stage of
diabetes and whether MDSCs from these OZ rats with late diabetes (late diabetic
SCs isolated and cultured in high-glucose medium [LD-SC]) differ from ED-SCs in
gene transcriptional phenotype and repair capacity., ED-SCs and LD-SCs were
compared by DNA microarray assays, and ED-SCs were incubated in聽vitro under
high-glucose conditions (ED-HG-SC). These three MDSC types were injected into
the corpora cavernosa of OZ rats with late diabetes (OZ/ED, OZ/LD, and OZ/ED-HG
rats, respectively). Untreated OZ and non-diabetic lean Zucker rats functioned
as controls. Two months later, rats were subjected to cavernosometry and the
penile shaft and corporal tissues were subjected to histopathology and DNA
microarray assays., In vivo erectile dysfunction assessment by Dynamic Infusion
Cavernosometry followed by histopathology marker analysis of the penile
tissues., Implanted ED-SCs and ED-HG-SCs improved corporal veno-occlusive
dysfunction, counteracted corporal decreases in the ratio of SMCs to collagen
and fat infiltration in rats with long-term T2D, and upregulated neuronal and
endothelial nitric oxide. LD-SCs acquired an inflammatory, pro-fibrotic,
oxidative, and dyslipidemic transcriptional phenotype and failed to repair the
corporal tissue., MDSCs from pre-diabetic rats injected into the corpora
cavernosa of rats with long-term T2D improve corporal veno-occlusive dysfunction
and the underlying histopathology. In contrast, MDSCs from rats with long-term
uncontrolled T2D are imprinted by the hyperglycemic and dyslipidemic milieu with
a noxious phenotype associated with an impaired tissue repair capacity. SCs
affected by diabetes could lack tissue repair efficacy as autografts and should
be reprogrammed in聽vitro or substituted by SCs from allogenic non-diabetic
sources.
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