title: Integrin-Linked Kinase Improves Functional Recovery of Diabetic Cystopathy and Mesenchymal Stem Cell Survival and Engraftment in Rats.
abstract: OBJECTIVE
  Diabetic cystopathy (DCP), characterized by peripheral neuropathy-associated bladder dysfunction, is a common urinary complication in patients with diabetes (~80%). Bone marrow mesenchymal stem cell (BMMSC) transplantation, a new and emerging regenerative therapy, provides a curative option for DCP. However, the application of this therapy is limited by the low survival rate and engraftment of transplanted stem cells. This study was undertaken to determine whether integrin-linked kinase (ILK) overexpression would improve stem cell survival and engraftment after BMMSC transplantation.
  
  
  METHODS
  Diabetes was induced in rats by injection of streptozotocin. ILK expression was detected by qRT-PCR and Western blot. Bladder function was measured by urodynamic analyses. Smooth-muscle regeneration and vascularization were evaluated by immunohistochemistry staining.
  
  
  RESULTS
  ILK overexpression by adenovirus promotes proliferation of BMMSCs in vitro. ILK overexpression enhanced the ability of BMMSCs to decrease the volume threshold for micturition and residual urine in the rats with diabetes. The contractile response of bladder strips, tissue structure of bladder and smooth-muscle regeneration/vascularization were also improved in the rats receiving ILK-modified BMMSCs.
  
  
  CONCLUSIONS
  Our data highlight the clinical potential of transplantation of gene-modified BMMSCs in the treatment of DCP, thereby serving as a rapid and effective first-line strategy to cure the bladder dysfunction resulting from long-term diabetes.
authors.affiliation: Department of Urology, Wuxi No. 3 People's Hospital, Wuxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Liucheng
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhengsen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Baixin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yinchao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Urology, Wuxi No. 3 People's Hospital, Wuxi, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: weizhongqing2249@126.com.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Wei
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology* / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D001750:Urinary Bladder, Neurogenic / Q000201:enzymology* / Q000209:etiology / Q000628:therapy*; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: bladder dysfunction; cellules souches mésenchymateuses; cystopathie diabétique; diabetic cystopathy; dysfonctionnement de la vessie; integrin-linked kinase; kinase liée aux intégrines; mesenchymal stem cells; régénération tissulaire; tissue regeneration