title: Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Takayanagi
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kataoka-Sasaki
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Masumori
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Kocsis
authors.affiliation: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.|Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honmou
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000473:pathology* / Q000628:therapy; D005724:Ganglia / Q000473:pathology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007001:Hypogastric Plexus / Q000378:metabolism; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration; D051101:Neurturin; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000294:innervation / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; C495053:NRTN protein, human; D051101:Neurturin
keywords: Erectile Dysfunction; Mesenchymal Stem Cells; Transplantation