AB159. Intravenous preload of mesenchymal stem cells rescues erectile function in a rat model of cavernous nerve injury

Objective: Erectile dysfunction (ED) following radical prostatectomy (RP) can occur as a result of cavernous nerve (CN) injury. Even with the surgical progress of CN preservation techniques and/or introduction of robot-assisted procedures, ED can occur after RP and decrease the patient’s quality of life. Therefore, it is necessary to pursue methods to reduce the number of ED patients. We previously reported the therapeutic efficacy of intravenous infusion of mesenchymal stem cells (MSCs) for neurological disorders. Currently, clinical trials for cerebral infarction (Phase III) and spinal cord injury (Phase II) are ongoing at our Hospital. The current hypothesis is that the key therapeutic mechanisms of transplanted MSCs in various models of nervous diseases are not only differentiation to neuronal and/or glial cells, but also secretion of neurotrophic factors that can provide for neuroprotection, induction of axonal sprouting and neovascularization. In this study we evaluated the potential preventive effects and mechanisms of intravenously preloaded MSCs for ED in a CN injury model.

Methods: The use of animals in this study was approved by the Animal Care and Use Committee of our institution. Male Sprague Dawley rats were used for this study. To assess erectile function, the CN was stimulated electrically, and we measured the intracavernous pressure (ICP) and arterial pressure (AP). ICP/AP and area under the curve of ICP (ICP-AUC) were used as indexes of erectile function. We measured the initial ICP/AP of pre-injury (normal) male SD rats. Then the rats were randomized into two groups (MSC and control groups). They were intravenously infused with MSCs (1.0×106 cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL DMEM) for sham control, respectively. Then CN injury was induced immediately after infusion. We measured ICP and AP at 1 hour and 2 weeks after transplantation. PKH26-labelled MSCs were used for tracking the transplanted MSCs. To investigate the expression levels of glia cell derived neurotrophic factor (GDNF) and neurturin mRNA in the major pelvic ganglia (MPG), we performed real-time quantitative RT-PCR.

Results: The reduction of ICP/AP and ICP-AUC in the MSC group was significantly lower than in the DMEM group (P<0.05; P<0.05) at 1 h. 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. 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; P<0.05).

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

Keywords: Mesenchymal stem cells (MSCs); cavernous nerve injury (CN injury); erectile dysfunction (ED)