title: Implantation of autologous urine derived stem cells expressing vascular endothelial growth factor for potential use in genitourinary reconstruction.
abstract: OBJECTIVE
  We evaluated the effects of vascular endothelial growth factor overexpression on urine derived stem cell survival and myogenic differentiation to determine whether these cells could be used as a novel cell source for genitourinary reconstruction.
  
  
  METHODS
  Urine derived stem cells were isolated from 31 urine samples of 6 healthy individuals 3 to 27 years old. Urine derived stem cells were infected with an adenoviral vector containing the mouse VEGF gene. These cells were then mixed with human umbilical vein endothelial cells (total 5×10(6)) in a collagen-I gel. These cell containing gels were subcutaneously implanted along with 6 other controls into 18 athymic mice. The grafts were assessed up to 28 days after injection for gross appearance and immunocytochemistry.
  
  
  RESULTS
  Vascular endothelial growth factor levels in the media from infected urine derived stem cell cultures reached a peak value on day 10 after infection. Grafts composed of urine derived stem cell/adenoviral vector containing the mouse VEGF gene and human umbilical vein endothelial cells were larger and better vascularized compared to uninfected urine derived stem cell control grafts. Additionally more implanted cells expressed human nuclear markers in the vascular endothelial growth factor expressing grafts. Vascular endothelial growth factor expressing grafts also contained more cells expressing the endothelial markers CD-31 and von Willebrand factor, and smooth muscle markers (α-smooth muscle actin, desmin and myosin). Also, more nerve fibers were present in urine derived stem cell/adenoviral vector containing mouse VEGF gene plus human umbilical vein endothelial cell grafts than in controls.
  
  
  CONCLUSIONS
  Vascular endothelial growth factor overexpression combined with human umbilical vein endothelial cells enhanced in vivo survival and myogenic differentiation of urine derived stem cells. Neovascularization and nerve regeneration were also enhanced within the implanted grafts.
authors.affiliation: Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Wu
authors.forename: Zhan
authors.initials: Z
authors.lastname: Wang
authors.forename: Shantaram
authors.initials: S
authors.lastname: Bharadwaj
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hodges
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D006801:Humans; D051379:Mice; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D014550:Urinary Incontinence, Stress / Q000601:surgery; D014556:Urine / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D014718:Vesico-Ureteral Reflux / Q000601:surgery; D055815:Young Adult
chemical_list: D042461:Vascular Endothelial Growth Factor A