The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model.
BACKGROUND
Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors.


OBJECTIVE
To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED.


METHODS
Twenty-eight male rats were induced to develop hyperlipidemia with a high-fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for 1 week, labeled with 5-ethynyl-2'-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate buffered saline (PBS). At 2 and 14 days post-transplantation, four rats in the HR + ADSC group were sacrificed for tracking of the transplanted cells. At 28 days post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function, and penile histology.


METHODS
Erectile function was assessed by intracavernous pressure (ICP) measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry.


RESULTS
Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean ICP/mean arterial pressure ratio was significantly lower in HR + PBS than in NR + PBS or HR + ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR + PBS than in HR + ADSC. Smooth muscle content was significantly higher in both HR groups than in NR.


CONCLUSIONS
Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED.
Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA.
Yun-Ching
YC
Huang
Hongxiu
H
Ning
Alan W
AW
Shindel
Thomas M
TM
Fandel
Guiting
G
Lin
Ahmed M
AM
Harraz
Tom F
TF
Lue
Ching-Shwun
CS
Lin
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006801:Humans; D006949:Hyperlipidemias / Q000473:pathology / Q000503:physiopathology*; D018783:Impotence, Vasculogenic / Q000473:pathology / Q000503:physiopathology*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000098:blood supply* / Q000294:innervation* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
D008077:Lipoproteins, LDL; D002784:Cholesterol; D052248:Nitric Oxide Synthase Type I