The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model

Yun Ching Huang, Hongxiu Ning, Alan W. Shindel, Thomas M. Fandel, Guiting Lin, Ahmed M. Harraz, Tom F. Lue, Ching Shwun Lin

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Abstract

Introduction.: 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. Aim.: 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. Main Outcome Measures.: 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. Huang Y-C, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, and Lin C-S. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model.

Original languageEnglish (US)
Pages (from-to)1391-1400
Number of pages10
JournalJournal of Sexual Medicine
Volume7
Issue number4 PART 1
DOIs
StatePublished - Apr 2010

Fingerprint

Erectile Dysfunction
Hyperlipidemias
Adipose Tissue
Stem Cells
Injections
Phosphates
Endothelium
Smooth Muscle
Endothelial Cells
Transplantation
Cell Tracking
Pressure
Nitric Oxide Synthase Type I

Keywords

  • Adipose Tissue-Derived Stem Cells
  • Erectile Dysfunction
  • Hyperlipidemia

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. / Huang, Yun Ching; Ning, Hongxiu; Shindel, Alan W.; Fandel, Thomas M.; Lin, Guiting; Harraz, Ahmed M.; Lue, Tom F.; Lin, Ching Shwun.

In: Journal of Sexual Medicine, Vol. 7, No. 4 PART 1, 04.2010, p. 1391-1400.

Research output: Contribution to journalArticle

Huang, Yun Ching ; Ning, Hongxiu ; Shindel, Alan W. ; Fandel, Thomas M. ; Lin, Guiting ; Harraz, Ahmed M. ; Lue, Tom F. ; Lin, Ching Shwun. / The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. In: Journal of Sexual Medicine. 2010 ; Vol. 7, No. 4 PART 1. pp. 1391-1400.
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AU - Huang, Yun Ching

AU - Ning, Hongxiu

AU - Shindel, Alan W.

AU - Fandel, Thomas M.

AU - Lin, Guiting

AU - Harraz, Ahmed M.

AU - Lue, Tom F.

AU - Lin, Ching Shwun

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N2 - Introduction.: 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. Aim.: 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. Main Outcome Measures.: 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. Huang Y-C, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, and Lin C-S. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model.

AB - Introduction.: 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. Aim.: 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. Main Outcome Measures.: 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. Huang Y-C, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, and Lin C-S. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model.

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