1152 PROMOTING MUSCLE AND NERVE REGENERATION AFTER HUMAN URINE-DERIVED STEM CELLS EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR FOR POTENTIAL USE IN TREATMENT OF STRESS URINARY INCONTINENCY

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence - Evaluation & Therapy1 Apr 20111152 PROMOTING MUSCLE AND NERVE REGENERATION AFTER HUMAN URINE-DERIVED STEM CELLS EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR FOR POTENTIAL USE IN TREATMENT OF STRESS URINARY INCONTINENCY GuiHua Liu, Shaofeng Wu, Shantaram Bharadwaj, Shay Soker, Anthony Atala, and Yuanyuan Zhang GuiHua LiuGuiHua Liu Winston-Salem, NC More articles by this author , Shaofeng WuShaofeng Wu Winston-Salem, NC More articles by this author , Shantaram BharadwajShantaram Bharadwaj Winston-Salem, NC More articles by this author , Shay SokerShay Soker Winston-Salem, NC More articles by this author , Anthony AtalaAnthony Atala Winston-Salem, NC More articles by this author , and Yuanyuan ZhangYuanyuan Zhang Winston-Salem, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.762AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stem cell therapy for stress urinary incontinency (SUI) has recently provided a promising alternative for repair of deficient urethral function. Muscle-derived stem cells, bone marrow-derived stem cells, and adipose-derived stem cells are regarded as candidates for this therapy. We have recently demonstrated that stem cells can be isolated from human urine and these urine-derived stem cells (USC) can give rise to mesodermal cell lineages, including muscle cells. The aim of this study was to determine the role of vascular endothelial growth factor (VEGF) expressing USC and endothelial cells on angiogenesis and grafted cell survival, growth, myogenic differentiation and innervations. METHODS USC were obtained from ten urine samples (five healthy individual donors, ages: 3–27). USC were infected with adenovirus containing the human VEGF gene (USC/Ad-VEGF). The USC (5×106 cells) in 500 μl collagen-I gel were subcutaneously implanted into 28 nude mice (two injections per mouse) and the animals were divided into five groups (G) as follows: G1, USC/Ad-VEGF plus endothelial cells; G2, USC/Ad-VEGF; G3, USC/Ad-GFP; G4, Skeletal muscle cells; G5, cell free as control. At day 28 after implantation, the grafts were assessed grossly and with immunohistochemistry for human nuclear markers, endothelial markers (CD 31 and vWF), muscle markers (alpha-smooth muscle actin, desmin and myosin) and nerve muscle makers(S-100, GFAP, Neurofilament). RESULTS Extensive vascularization was observed in G1 (USC/Ad-VEGF plus endothelial cells) compared to the non-VEGF controls, and immunofluorescent staining for muscle markers revealed that the grafts in this group contained large numbers of cells with a myogenic phenotype. Additionally, there were significantly more implanted cells expressing human nuclear markers and endothelial markers in group 1. Finally, a larger number of peripheral nerve fibers were observed in the grafts in the USC/Ad-VEGF plus endothelial cells group. However, a few new nerve fibers expressed human nuclear markers, suggesting that most of these regenerated nerve fibers are derived from the host nerve tissue. CONCLUSIONS VEGF expression by USC enhanced cell survival as well as endothelial and myogenic differentiation of USC. In addition, VEGF expression appeared to significantly increase nerve regeneration as well. This approach might have important clinical implications for the development of novel cell therapies for the correction of SUI. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e462 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information GuiHua Liu Winston-Salem, NC More articles by this author Shaofeng Wu Winston-Salem, NC More articles by this author Shantaram Bharadwaj Winston-Salem, NC More articles by this author Shay Soker Winston-Salem, NC More articles by this author Anthony Atala Winston-Salem, NC More articles by this author Yuanyuan Zhang Winston-Salem, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...