title: Intracavernous delivery of clonal mesenchymal stem cells restores erectile function in a mouse model of cavernous nerve injury.
abstract: BACKGROUND
  Recently, much attention has focused on stem cell therapy; bone marrow-derived stem cells (BMSCs) are one of the most studied mesenchymal stem cells used in the field of erectile dysfunction (ED). However, a major limitation for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes.
  
  
  OBJECTIVE
  We investigated the effectiveness of mouse clonal BMSCs obtained from a single colony by using subfractionation culturing method (SCM) for erectile function in a mouse model of cavernous nerve injury (CNI).
  
  
  METHODS
  Twelve-week-old C57BL/6J mice were divided into four groups: sham operation group, bilateral CNI group receiving a single intracavernous (IC) injection of phosphate-buffered saline (20 μL) or clonal BMSCs (3 × 10(5) cells/20 μL), and receiving a single intraperitoneal (IP) injection of clonal BMSCs (3 × 10(5) cells/20 μL).
  
  
  METHODS
  The clonal BMSC line was analyzed for cell-surface epitopes by using fluorescence-activated cell sorting and for differentiation potential. Two weeks after CNI and treatment, erectile function was measured by electrically stimulating the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis.
  
  
  RESULTS
  Clonal BMSCs expressed cell surface markers for mesenchymal stem cells and were capable of differentiating into several lineages, including adipogenic, osteogenic, and chondrogenic cells. Both IC and IP injections of clonal BMSCs significantly restored cavernous endothelial and smooth muscle content, and penile nNOS and neurofilament content in CNI mice. IC injection of clonal BMSCs induced significant recovery of erectile function, which reached 90-100% of the sham control values, whereas IP injection of clonal BMSCs partially restored erectile function.
  
  
  CONCLUSIONS
  We established a homogeneous population of mouse clonal BMSCs using SCM; clonal BMSCs successfully restored erectile function in CNI mice. The homogeneous nature of clonal mesenchymal stem cells may allow their clinical applications.
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: Da-Ham
authors.initials: DH
authors.lastname: Kim
authors.forename: Kang Moon
authors.initials: KM
authors.lastname: Song
authors.forename: Tacghee
authors.initials: T
authors.lastname: Yi
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
authors.forename: Sun U
authors.initials: SU
authors.lastname: Song
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000209:etiology* / Q000601:surgery*; D007267:Injections; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000201:enzymology / Q000294:innervation* / Q000601:surgery; D059348:Peripheral Nerve Injuries / Q000150:complications*; D012038:Regeneration
chemical_list: D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse
keywords: Cavernous Nerve Injury; Clonal Mesenchymal Stem Cell; Erectile Dysfunction; Mouse Model of Erectile Dysfunction; Stem Cell Therapy