PMID- 20141586 OWN - NLM STAT- MEDLINE DCOM- 20100830 LR - 20211020 IS - 1743-6109 (Electronic) IS - 1743-6095 (Print) IS - 1743-6095 (Linking) VI - 7 IP - 4 Pt 1 DP - 2010 Apr TI - The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. PG - 1391-400 LID - 10.1111/j.1743-6109.2009.01697.x [doi] 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. FAU - Huang, Yun-Ching AU - Huang YC AD - Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA. FAU - Ning, Hongxiu AU - Ning H FAU - Shindel, Alan W AU - Shindel AW FAU - Fandel, Thomas M AU - Fandel TM FAU - Lin, Guiting AU - Lin G FAU - Harraz, Ahmed M AU - Harraz AM FAU - Lue, Tom F AU - Lue TF FAU - Lin, Ching-Shwun AU - Lin CS LA - eng GR - R01 DK045370/DK/NIDDK NIH HHS/United States GR - R37 DK045370/DK/NIDDK NIH HHS/United States GR - R37 DK045370-15/DK/NIDDK NIH HHS/United States GR - DK045370/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100205 PL - Netherlands TA - J Sex Med JT - The journal of sexual medicine JID - 101230693 RN - 0 (Lipoproteins, LDL) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) SB - IM MH - Adipose Tissue/*cytology MH - Animals MH - Blood Pressure MH - Blood Vessels/pathology/physiopathology MH - Cholesterol/blood MH - Diet, Atherogenic MH - *Disease Models, Animal MH - Humans MH - Hyperlipidemias/pathology/*physiopathology MH - Impotence, Vasculogenic/pathology/*physiopathology MH - Lipoproteins, LDL/blood MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Nerve Fibers/pathology/physiology MH - Nitric Oxide Synthase Type I/metabolism MH - Penile Erection/physiology MH - Penis/*blood supply/*innervation/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Young Adult PMC - PMC3163604 MID - NIHMS317705 EDAT- 2010/02/10 06:00 MHDA- 2010/08/31 06:00 PMCR- 2011/08/29 CRDT- 2010/02/10 06:00 PHST- 2010/02/10 06:00 [entrez] PHST- 2010/02/10 06:00 [pubmed] PHST- 2010/08/31 06:00 [medline] PHST- 2011/08/29 00:00 [pmc-release] AID - S1743-6095(15)32981-7 [pii] AID - 10.1111/j.1743-6109.2009.01697.x [doi] PST - ppublish SO - J Sex Med. 2010 Apr;7(4 Pt 1):1391-400. doi: 10.1111/j.1743-6109.2009.01697.x. Epub 2010 Feb 5.