Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury

J Sex Med. 2015 Aug;12(8):1713-21. doi: 10.1111/jsm.12957. Epub 2015 Jul 24.

Abstract

Introduction: We evaluated the potential preventive effects and mechanisms of intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction (ED) in a cavernous nerve (CN) injury model.

Methods: Male Sprague-Dawley (SD) rats were used for this study. Rats were randomized into two groups. One group was intravenously preloaded with MSCs (1.0 × 10(6) cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL Dulbecco's modified Eagle's medium [DMEM]) for sham control, respectively. Crushed CN injury was induced immediately after infusion. The surgeon was blind to the experimental conditions (MSC or medium).

Main outcome measures: To assess erectile function, we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1 hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre-injury (normal) male SD rats, they were randomized into the two groups and infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To investigate the mRNA expression levels of neurotrophins in the major pelvic ganglia (MPG), we performed real-time quantitative real-time polymerase chain reaction.

Results: The reduction of ICP/AP and area under the curve of ICP (ICP-AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. Glia cell-derived neurotrophic factor (GDNF) and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P < 0.01, 0.05).

Conclusion: Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.

Keywords: Erectile Dysfunction; Mesenchymal Stem Cells; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Erectile Dysfunction / pathology*
  • Erectile Dysfunction / therapy
  • Ganglia / pathology*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Hypogastric Plexus / metabolism
  • Male
  • Nerve Crush
  • Nerve Regeneration
  • Neurturin
  • Penile Erection / drug effects*
  • Penile Erection / physiology
  • Penis / innervation
  • Penis / pathology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • NRTN protein, human
  • Neurturin