title: Human urine-derived stem cells alone or genetically-modified with FGF2 Improve type 2 diabetic erectile dysfunction in a rat model.
abstract: OBJECTIVE
  The aim of this study was to determine the possibility of improving erectile dysfunction using cell therapy with either human urine-derived stem cells (USCs) or USCs genetically-modified with FGF2 in a type 2 diabetic rat model.
  
  
  METHODS
  Human USCs were collected from 3 healthy donors. USCs were transfected with FGF2 (USCs-FGF2). Sixty-five SD male rats were divided into five groups (G). A control group of normal rats (G1, n = 10), and four other test groups of type 2 diabetic erectile dysfunction rats: PBS as a negative control (G2, n = 10), USCs (G3, n = 15), lentivirus-FGF2 (G4, n = 15), and USCs-FGF2 (G5, n = 15). Diabetes was induced in the rats via a high fat diet for 28 days and a subsequent intraperitoneal injection of streptozotocin (35 mg/kg). Erectile dysfunction was screened with apomorphine (100 μg/kg). Cell injections in the test groups (G2-G5) occurred directly into the corpora cavernosa. The implanted cells were tracked at 7 days (n = 5 animals/G) and 28 days (n = 10 animals/G) post injection. Mean arterial pressure (MAP), intracavernosal pressure (ICP), expression of endothelial markers (CD31, VEGF and eNOS), smooth muscle markers (desmin and smoothelin), histological changes and erectile function were assessed for each group.
  
  
  RESULTS
  USCs expressed mesenchymal stem cell markers, and secreted a number of proangiogenic growth factors. USCs expressed endothelial cell markers (CD31 and vWF) after transfection with FGF2. Implanted USCs or USCs-FGF2 displayed a significantly raised ICP and ICP/MAP ratio (p<0.01) 28 days after intracavernous injection. Although few cell were detected within the implanted sites, histological and western blot analysis demonstrated an increased expression of endothelial and smooth muscle markers within the cavernous tissue following USC or USC-FGF2 injection.
  
  
  CONCLUSIONS
  The paracrine effect of USCs or USCs-FGF2 induced improvement of erectile function in type 2 diabetic rats by recruiting resident cells and increasing the endothelial expression and contents of smooth muscle.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ouyang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of 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, People's Republic of 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, People's Republic of China.
authors.forename: Shenfu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.affiliation: Reproductive Medicine Center, the Key Laboratory for Reproductive Medicine of Guangdong Province, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Bian
authors.affiliation: Shanghai Institute of Andrology, Renji Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China; Wake Forest Institute of Regenerative Medicine, Wake Forest University, Winston Salem, North Carolina, United States of America.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of endocrinology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Gene Engineering of Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
authors.affiliation: Department of Andrology, Center for Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; Wake Forest Institute of Regenerative Medicine, Wake Forest University, Winston Salem, North Carolina, United States of America.
authors.forename: Guihua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Wake Forest Institute of Regenerative Medicine, Wake Forest University, Winston Salem, North Carolina, United States of America.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Deng
mesh_terms: D000328:Adult; D000818:Animals; D048909:Diabetes Complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D007172:Erectile Dysfunction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D064593:Heterografts; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic
chemical_list: D016222:Fibroblast Growth Factor 2