title: Maximum efficacy of mesenchymal stem cells in rat model of renal ischemia-reperfusion injury: renal artery administration with optimal numbers.
abstract: BACKGROUND
  Despite the potential therapeutic benefits, cell therapy in renal ischemia-reperfusion (I/R) injury is currently limited by low rates of cell engraftment after systemic delivery. In this study, we investigate whether locally administration through renal artery can enhance the migration and therapeutic potential of mesenchymal stem cells (MSCs) in ischemic kidney.
  
  
  METHODS
  The model of renal I/R injury was induced by 45 min occlusion of the left renal pedicle and right nephrectomy in rat. Followed by reperfusion, graded doses of CM-Dil labeled MSCs were implanted via three routes: tail vein (TV), carotid artery (CA), and renal artery (RA). Renal blood flow was evaluated by color and spectral Doppler ultrasound at 1 h and 24 h post-I/R. All the samples were collected for analysis at 24 h post-I/R.
  
  
  RESULTS
  After injection of 1×10(6) MSCs, RA group showed obviously increased renal retention of grafted MSCs compared with TV and CA group; however, the renal function was even further deteriorated. When graded doses of MSCs, the maximal therapeutic efficiency was achieved with renal artery injection of 1×10(5) MSCs, which was significantly better than TV and CA group of 1×10(6) MSCs. In addition, further fluorescent microscopic and ultrasonic examination confirmed that the aggravated renal dysfunction in RA group was due to renal hypoperfusion caused by cell occlusion.
  
  
  CONCLUSIONS
  Administration route and dosage are two critical factors determining the efficiency of cell therapy and 1×10(5) MSCs injected through renal artery produces the most dramatic improvement in renal function and morphology in rat model of renal I/R injury.
authors.affiliation: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jieru
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Rende
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Ultrasonography, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Blood Purification Center, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Ding
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007267:Injections; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012077:Renal Artery / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D014463:Ultrasonography