Implantation of Autologous Urine Derived Stem Cells Expressing Vascular Endothelial Growth Factor for Potential Use in Genitourinary Reconstruction

No AccessJournal of UrologyPediatric Urology1 Aug 2011Implantation of Autologous Urine Derived Stem Cells Expressing Vascular Endothelial Growth Factor for Potential Use in Genitourinary Reconstruction Shaofeng Wu, Zhan Wang, Shantaram Bharadwaj, Steven J. Hodges, Anthony Atala, and Yuanyuan Zhang Shaofeng WuShaofeng Wu Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina , Zhan WangZhan Wang Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina , Shantaram BharadwajShantaram Bharadwaj Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina , Steven J. HodgesSteven J. Hodges Department of Urology, Wake Forest University Health Sciences, Winston-Salem, North Carolina , Anthony AtalaAnthony Atala Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina , and Yuanyuan ZhangYuanyuan Zhang Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina View All Author Informationhttps://doi.org/10.1016/j.juro.2011.03.152AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: 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. Materials and 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 × 106) 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. References 1 : Cystoscopic autogenous fat injection treatment of vesicoureteral reflux in spinal cord injury. J Am Paraplegia Soc1994; 17: 50. Google Scholar 2 : Long-term outcome of the endoscopic correction of vesico-ureteric reflux: a comparison of injected substances. BJU Int2004; 94: 381. 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Link, Google Scholar © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byOsborn S and Kurzrock E (2018) Bioengineered Bladder Tissue—Close but Yet So Far!Journal of Urology, VOL. 194, NO. 3, (619-620), Online publication date: 1-Sep-2015. Volume 186Issue 2August 2011Page: 640-647 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordsvesico-ureteral refluxangiogenesis inducing agentsstem cellstissue therapyreceptors, vascular endothelial growth factorAcknowledgmentsKarl-Erik Andersson provided valuable comments. Ms. Karen Klein and Dr. Jennifer Olson supplied editorial assistance. Dr. Guihua Liu provided technical assistance with immunofluorescent staining of regenerated nerve tissue.MetricsAuthor Information Shaofeng Wu Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina More articles by this author Zhan Wang Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina More articles by this author Shantaram Bharadwaj Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina More articles by this author Steven J. Hodges Department of Urology, Wake Forest University Health Sciences, Winston-Salem, North Carolina More articles by this author Anthony Atala Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina More articles by this author Yuanyuan Zhang Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina More articles by this author Expand All Advertisement PDF downloadLoading ...