title: Urethral reconstruction with autologous urine-derived stem cells seeded in three-dimensional porous small intestinal submucosa in a rabbit model.
abstract: Urethral reconstruction is one of the great surgical challenges for urologists. A cell-based tissue-engineered urethra may be an alternative for patients who have complicated long strictures and need urethral reconstruction. Here, we demonstrated the feasibility of using autologous urine-derived stem cells (USCs) seeded on small intestinal submucosa (SIS) to repair a urethral defect in a rabbit model.
  
  
  
  Autologous USCs were obtained and characterized, and their capacity to differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs) was tested. Then, USCs were labeled with PKH67, seeded on SIS, and transplanted to repair a urethral defect. The urethral defect model was surgically established in New Zealand white male rabbits. A ventral urethral gap was created, and the urethral mucosa was completely removed, with a mean rabbit penile urethra length of 2 cm. The urethral mucosal defect was repaired with a SIS scaffold (control group: SIS with no USCs; experimental group: autologous USC-seeded SIS; n = 12 for each group). A series of tests, including a retrograde urethrogram, histological analysis, and immunofluorescence, was undertaken 2, 3, 4, and 12 weeks after the operation to evaluate the effect of the autologous USCs on urethral reconstruction.
  
  
  
  Autologous USCs could be easily collected and induced to differentiate into UCs and SMCs. In addition, the urethral caliber, speed of urothelial regeneration, content of smooth muscle, and vessel density were significantly improved in the group with autologous USC-seeded SIS. Moreover, inflammatory cell infiltration and fibrosis were found in the control group with only SIS, but not in the experimental autologous USC-seeded SIS group. Furthermore, immunofluorescence staining demonstrated that the transplanted USCs differentiated into UCs and SMCs in vivo.
  
  
  
  Autologous USCs can be used as an alternative cell source for cell-based tissue engineering for urethral reconstruction.
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China.|Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China.
authors.forename: Yangcai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
authors.forename: Geng
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China.
authors.forename: Lianju
authors.initials: L
authors.lastname: Shen
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China.
authors.forename: Chunlan
authors.initials: C
authors.lastname: Long
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: He
authors.affiliation: Research Institute for Uronephrology, Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
authors.forename: Denis
authors.initials: D
authors.lastname: Butnaru
authors.affiliation: Biomedical Research Department of Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
authors.forename: Lyundup
authors.initials: L
authors.lastname: Alexey
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. deyingzhang2016@163.com.|Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Chongqing, 400014, China. deyingzhang2016@163.com.
authors.forename: Deying
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. guanghuiwei2016@126.com.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wei
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007421:Intestine, Small / Q000637:transplantation; D032389:Myocytes, Smooth Muscle / Q000637:transplantation; D011817:Rabbits; D012038:Regeneration / Q000235:genetics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D023822:Tissue Engineering; D014182:Transplantation, Autologous; D014521:Urethra / Q000254:growth & development* / Q000293:injuries / Q000473:pathology; D014522:Urethral Diseases / Q000473:pathology / Q000628:therapy* / Q000652:urine
keywords: Tissue engineering; Urethral reconstruction; Urine-derived stem cells