title: Intracavernous delivery of stromal vascular fraction restores erectile function through production of angiogenic factors in a mouse model of cavernous nerve injury.
abstract: BACKGROUND
  Erectile dysfunction (ED) is a major complication of radical prostatectomy. Men with radical prostatectomy-induced ED respond less positively to oral phosphodiesterase-5 inhibitors.
  
  
  OBJECTIVE
  The study aims to examine whether and how stromal vascular fraction (SVF) restores erectile function in mice with cavernous nerve injury (CNI).
  
  
  METHODS
  Twelve-week-old male C57BL/6J mice were used and the animals were distributed into five groups: sham operation group and CNI group receiving a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 × 10(4) , 1 × 10(5) , or 3 × 10(5) cells/20 μL, respectively). SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice.
  
  
  METHODS
  Two weeks after injection, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to platelet/endothelial cell adhesion molecule-1, phosphohistone H3, and phosphorylated endothelial nitric oxide synthase (phospho-eNOS). We also performed Western blot for angiopoietin-1 (Ang-1), vascular endothelial growth factor-A, hepatocyte growth factor, phospho-eNOS, and eNOS in the corpus cavernosum tissue.
  
  
  RESULTS
  Local delivery of SVF restored erectile function in a dose-dependent manner in CNI mice. The highest erectile response was noted at a dose of 3 × 10(5) cells, for which the response was comparable with that in the sham operation group. Local delivery of SVF significantly increased the expression of angiogenic factor proteins and induced cavernous endothelial cell proliferation and eNOS phosphorylation compared with that in the PBS-treated CNI group. SVF-induced promotion of cavernous angiogenesis and erectile function was diminished in the presence of soluble antibody to Tie2, a receptor tyrosine kinase of Ang-1.
  
  
  CONCLUSIONS
  Secretion of angiogenic factors from SVF is an important mechanism by which SVF induces cavernous endothelial regeneration and restores erectile function. These findings suggest that cavernous endothelial regeneration by using SVF may represent a promising treatment strategy for radical prostatectomy-induced ED.
authors.affiliation: National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
authors.forename: Kang-Moon
authors.initials: KM
authors.lastname: Song
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Jin
authors.forename: Jin-Mi
authors.initials: JM
authors.lastname: Park
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Mi-Hye
authors.initials: MH
authors.lastname: Kwon
authors.forename: Ki-Dong
authors.initials: KD
authors.lastname: Kwon
authors.forename: Dulguun
authors.initials: D
authors.lastname: Batbold
authors.forename: Guo Nan
authors.initials: GN
authors.lastname: Yin
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D007172:Erectile Dysfunction / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010413:Penis / Q000098:blood supply / Q000294:innervation; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012038:Regeneration; D017154:Stromal Cells / Q000637:transplantation*; D020196:Trauma, Nervous System / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III
keywords: Angiogenesis; Cavernous Nerve Injury; Erectile Dysfunction; Stem Cells; Stromal Vascular Fraction