PMID- 24460735 OWN - NLM STAT- MEDLINE DCOM- 20150402 LR - 20221207 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 18 IP - 3 DP - 2014 Mar TI - Engineering of pre-vascularized urethral patch with muscle flaps and hypoxia-activated hUCMSCs improves its therapeutic outcome. PG - 434-43 LID - 10.1111/jcmm.12157 [doi] AB - Tissue engineering has brought new hopes for urethral reconstruction. However, the absence of pre-vascularization and the subsequent degradation of materials often lead to the failure of in vivo application. In this study, with the assistance of hypoxia-activated human umbilical cord mesenchymal stem cells (hUCMSCs), pedicled muscle flaps were used as materials and pre-incubated in ventral penile subcutaneous cavity of rabbit for 3 weeks to prepare a pre-vascularized urethral construct. We found that small vessels and muscle fibres were scattered in the construct after 3 weeks' pre-incubation. The construct presented a fibrous reticular structure, which was similar to that of the corpus spongiosum under microscope examination. The produced constructs were then used as a patch graft for reconstruction of the defective rabbit urethra (experimental group), natural muscular patch was used as control (control group). Twelve weeks after the reconstructive surgery, urethrography and urethroscope inspections showed wide calibres of the reconstructed urethra in the experimental group. Histopathological studies revealed that fibrous connective tissues and abundant muscle fibres constituted the main body of the patch-grafted urethra. In contrast, in the control group, only adipose tissue was found in the stenosis-reconstructed urethra, replacing the originally grafted muscular tissue. To our knowledge, this is the first report that successfully constructed a pre-vascularized urethral construct by using hypoxia-activated hUCMSC and pedicled muscle flaps. More importantly, the pre-vascularized construct showed a good performance in urethral reconstruction when applied in vivo. The study provided a novel strategy for tissue engineering of pre-vascularized urethral construct for the defective urethra, representing a further advancement in urethral reconstruction. CI - (c) 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. FAU - Sun, Dongchong AU - Sun D AD - Department of Urology, People's Liberation Army General Hospital, Beijing, China. FAU - Yang, Yong AU - Yang Y FAU - Wei, Zhitao AU - Wei Z FAU - Xu, Yong AU - Xu Y FAU - Zhang, Xu AU - Zhang X FAU - Hong, Baofa AU - Hong B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140125 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Cytokines) SB - IM MH - Angiogenesis Inducing Agents/metabolism MH - Animals MH - Blotting, Western MH - Cell Hypoxia MH - Cell Separation MH - Cytokines/metabolism MH - Humans MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - Muscles/*blood supply MH - Rabbits MH - Radiography MH - Plastic Surgery Procedures MH - Subcutaneous Tissue/physiology MH - Surgical Flaps/*blood supply MH - Tissue Engineering/*methods MH - Umbilical Cord/*cytology MH - Urethra/*blood supply/diagnostic imaging/surgery PMC - PMC3955150 OTO - NOTNLM OT - hUCMSC OT - pedicled muscle flaps OT - tissue engineering OT - urethral reconstruction EDAT- 2014/01/28 06:00 MHDA- 2015/04/04 06:00 PMCR- 2014/03/01 CRDT- 2014/01/28 06:00 PHST- 2013/05/17 00:00 [received] PHST- 2013/09/09 00:00 [accepted] PHST- 2014/01/28 06:00 [entrez] PHST- 2014/01/28 06:00 [pubmed] PHST- 2015/04/04 06:00 [medline] PHST- 2014/03/01 00:00 [pmc-release] AID - 10.1111/jcmm.12157 [doi] PST - ppublish SO - J Cell Mol Med. 2014 Mar;18(3):434-43. doi: 10.1111/jcmm.12157. Epub 2014 Jan 25.