title: Transplantation of Human Urine-Derived Stem Cells Transfected with Pigment Epithelium-Derived Factor to Protect Erectile Function in a Rat Model of Cavernous Nerve Injury.
abstract: The aim of this study was to investigate whether intracavernous injection of urine-derived stem cells (USCs) or USCs genetically modified with pigment epithelium-derived factor (PEDF) could protect the erectile function and cavernous structure in a bilateral cavernous nerve injury-induced erectile dysfunction (CNIED) rat model. USCs were cultured from the urine of six healthy male donors. Seventy-five rats were randomly divided into five groups ( n = 15 per group): sham, bilateral cavernous nerve (CN) crush injury (BCNI), USC, USCGFP+, and USCGFP/PEDF+groups. The sham group received only laparotomy without CN crush injury and intracavernous injection with phosphate-buffered saline (PBS). All of the other groups were subjected to BCNI and intracavernous injection with PBS, USCs, USCsGFP+, or USCsGFP/PEDF+, respectively. The total intracavernous pressure (ICP) and the ratio of ICP to mean arterial pressure (ICP/MAP) were recorded. The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue. The USC and USCGFP/PEDF+groups displayed more significantly enhanced ICP and ICP/MAP ratio ( p < 0.05) 28 days after cell transplantation. Immunohistochemistry (IHC) and Western blot analysis demonstrated that the protection of erectile function and the cavernous structure by USCsGFP/PEDF+was associated with an increased number of nNOS-positive fibers within the penile dorsal nerves, improved expression of endothelial markers (CD31 and eNOS) and a smooth muscle marker (smoothelin), an enhanced smooth muscle to collagen ratio, decreased expression of transforming growth factor-β1 (TGF-β1), and decreased cell apoptosis in the cavernous tissue. The paracrine effect of USCs and USCsGFP/PEDF+prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving endothelial cell function, increasing the smooth muscle content, and decreasing fibrosis and cell apoptosis in the cavernous tissue.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Qiyun
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Dayu
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine Research Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Urology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Bian
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Xiangzhou
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xia
authors.affiliation: Reproductive Medicine Research Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Reproductive Medicine Research Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Wake Forest Institute of Regenerative Medicine, Wake Forest University, Winston Salem, NC, USA.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000473:pathology / Q000628:therapy*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014556:Urine / Q000166:cytology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D009124:Muscle Proteins; D009414:Nerve Growth Factors; D052250:Nitric Oxide Synthase Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015843:Serpins; D053773:Transforming Growth Factor beta1; D000099174:Pigment Epithelium-Derived Factor; C491051:Smtn protein, rat
keywords: Cavernous never injury; Erectile dysfunction (ED); Pigment epithelium-derived factor (PEDF); Urine-derived stem cells (USCs)