title: Intracavernous delivery of freshly isolated stromal vascular fraction rescues erectile function by enhancing endothelial regeneration in the streptozotocin-induced diabetic mouse.
abstract: BACKGROUND
  Men with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors.
  
  
  OBJECTIVE
  To examine whether and how freshly isolated stromal vascular fraction (SVF) promotes cavernous endothelial regeneration and restores erectile function in diabetic animals.
  
  
  METHODS
  Eight-week-old C57BL/6J mice were used. Diabetes was induced by intraperitoneal injection of streptozotocin. SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice. At 8 weeks after the induction of diabetes, the animals were divided into six groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 × 10(4) cells, 1 × 10(5) cells, or 2 × 10(5) cells/20 µL, respectively).
  
  
  METHODS
  Two weeks later, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to CD31, CD34, phosphohistone H3, phospho-endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor-A (VEGF-A). We also performed Western blot for phospho-eNOS and eNOS, and determined cyclic guanosine monophosphate (cGMP) concentration in the corpus cavernosum tissue.
  
  
  RESULTS
  Significant improvement in erectile function was noted in diabetic mice treated with SVF at concentrations of 1 × 10(5) and 2 × 10(5) cells, which reached up to 82% of the control values. Local delivery of SVF significantly increased cavernous endothelial cell proliferation, eNOS phosphorylation, and cGMP expression compared with that in the untreated group and the PBS-treated diabetic group. Intracavernous injection of SVF increased cavernous VEGF-A expression and induced recruitment of CD34(+)CD31(-) progenitor cells. Some SVF underwent differentiation into cavernous endothelial cells. SVF-induced promotion of cavernous angiogenesis and erectile function was abolished in the presence of VEGF-Trap, a soluble VEGF-A neutralizing antibody.
  
  
  CONCLUSIONS
  The results support the concept of cavernous endothelial regeneration by use of SVF as a curative therapy for diabetic ED.
authors.affiliation: National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea.
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.forename: Munkhbayar
authors.initials: M
authors.lastname: Tumurbaatar
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Jin
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.forename: Mi-Hye
authors.initials: MH
authors.lastname: Kwon
authors.forename: Shuguang
authors.initials: S
authors.lastname: Piao
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Guo Nan
authors.initials: GN
authors.lastname: Yin
authors.forename: Kang-Moon
authors.initials: KM
authors.lastname: Song
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Koh
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D006152:Cyclic GMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000502:physiology*; D004822:Epididymis / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology; D018919:Neovascularization, Physiologic; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000098:blood supply / Q000378:metabolism / Q000601:surgery*; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism; D017154:Stromal Cells / Q000637:transplantation*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP