The Effect of Intracavernous Injection of Adipose Tissue-Derived Stem Cells on Hyperlipidemia-Associated Erectile Dysfunction in a Rat Model

Authors

  • Yun-Ching Huang MD,

    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
    2. Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chia-Yi, Chang Gung University College of Medicine, Taiwan;
    3. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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  • Hongxiu Ning PhD,

    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
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  • Alan W. Shindel MD,

    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
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  • Thomas M. Fandel MD,

    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
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  • Guiting Lin MD, PhD,

    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
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  • Ahmed M. Harraz MD,

    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
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  • Tom F. Lue MD,

    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
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  • Ching-Shwun Lin PhD

    Corresponding author
    1. Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA;
      Ching-Shwun Lin, PhD, Department of Urology, University of California, 533 Parnassus Avenue, Room 212, San Francisco, CA 94143-0738, USA. Tel: (1) 415-476-3800; Fax: (1) 415-476-3803; E-mail: clin@urology.ucsf.edu
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Ching-Shwun Lin, PhD, Department of Urology, University of California, 533 Parnassus Avenue, Room 212, San Francisco, CA 94143-0738, USA. Tel: (1) 415-476-3800; Fax: (1) 415-476-3803; E-mail: clin@urology.ucsf.edu

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. J Sex Med 2010;7:1391–1400.

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