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

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

Author information

1
Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
2
Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
3
Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
4
Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, USA.

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

PMID:
26211660
DOI:
10.1111/jsm.12957
[Indexed for MEDLINE]
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