Maximum Efficacy of Mesenchymal Stem Cells in Rat Model of Renal Ischemia-Reperfusion Injury: Renal Artery Administration with Optimal Numbers

被引:34
作者
Cai, Jieru [1 ]
Yu, Xiaofang [1 ]
Xu, Rende [2 ]
Fang, Yi [1 ]
Qian, Xiaoqin [3 ]
Liu, Shaopeng [1 ]
Teng, Jie [4 ]
Ding, Xiaoqiang [1 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Dept Nephrol, Shanghai 200433, Peoples R China
[2] Shanghai Jiao Tong Univ, Renji Hosp, Dept Cardiol, Shanghai 200030, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Dept Ultrasonog, Shanghai 200433, Peoples R China
[4] Fudan Univ, Zhongshan Hosp, Blood Purificat Ctr, Shanghai 200433, Peoples R China
来源
PLOS ONE | 2014年 / 9卷 / 03期
关键词
ACUTE KIDNEY INJURY; EFFICIENCY; SURVIVAL; DELIVERY; THERAPY; FAILURE;
D O I
10.1371/journal.pone.0092347
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Backgrounds: 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 1x10(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 1x10(5) MSCs, which was significantly better than TV and CA group of 1x10(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. Conclusion: Administration route and dosage are two critical factors determining the efficiency of cell therapy and 1x10(5) MSCs injected through renal artery produces the most dramatic improvement in renal function and morphology in rat model of renal I/R injury.
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相关论文
共 29 条
[1]   Intraparenchymal Injection of Bone Marrow Mesenchymal Stem Cells Reduces Kidney Fibrosis After Ischemia-Reperfusion in Cyclosporine-Immunosuppressed Rats [J].
Alfarano, C. ;
Roubeix, C. ;
Chaaya, R. ;
Ceccaldi, C. ;
Calise, D. ;
Mias, C. ;
Cussac, D. ;
Bascands, J. L. ;
Parini, A. .
CELL TRANSPLANTATION, 2012, 21 (09) :2009-2019
[2]   Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4 [J].
Allam, Ramanjaneyulu ;
Scherbaum, Christina Rebecca ;
Darisipudi, Murthy Narayana ;
Mulay, Shrikant R. ;
Haegele, Holger ;
Lichtnekert, Julia ;
Hagemann, Jan Henrik ;
Rupanagudi, Khader Valli ;
Ryu, Mi ;
Schwarzenberger, Claudia ;
Hohenstein, Bernd ;
Hugo, Christian ;
Uhl, Bernd ;
Reichel, Christoph A. ;
Krombach, Fritz ;
Monestier, Marc ;
Liapis, Helen ;
Moreth, Kristin ;
Schaefer, Liliana ;
Anders, Hans-Joachim .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2012, 23 (08) :1375-1388
[3]   Poor Cell Survival Limits the Beneficial Impact of Mesenchymal Stem Cell Transplantation on Acute Kidney Injury [J].
Burst, Volker R. ;
Gillis, Meyke ;
Puetsch, Florian ;
Herzog, Ruth ;
Fischer, Juergen H. ;
Heid, Petra ;
Mueller-Ehmsen, Jochen ;
Schenk, Kerstin ;
Fries, Jochen W. U. ;
Baldamus, Conrad A. ;
Benzing, Thomas .
NEPHRON EXPERIMENTAL NEPHROLOGY, 2010, 114 (03) :E107-E116
[4]   Cell Delivery Routes for Stem Cell Therapy to the Heart: Current and Future Approaches [J].
Campbell, Niall G. ;
Suzuki, Ken .
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, 2012, 5 (05) :713-726
[5]  
da Cunha MGMCM, 2013, EUR SURG RES, V51, P58, DOI 10.1159/000354389
[6]   Mesenchymal Stem Cells Infusion Prevents Acute Cellular Rejection in Rat Kidney Transplantation [J].
De Martino, M. ;
Zonta, S. ;
Rampino, T. ;
Gregorini, M. ;
Frassoni, F. ;
Piotti, G. ;
Bedino, G. ;
Cobianchi, L. ;
Dal Canton, A. ;
Dionigi, P. ;
Alessiani, M. .
TRANSPLANTATION PROCEEDINGS, 2010, 42 (04) :1331-1335
[7]   Update on mechanisms of ischemic acute kidney injury [J].
Devarajan, Prasad .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (06) :1503-1520
[8]   Ischemia and reperfusion-from mechanism to translation [J].
Eltzschig, Holger K. ;
Eckle, Tobias .
NATURE MEDICINE, 2011, 17 (11) :1391-1401
[9]   Acute Kidney Injury in a Chinese Hospitalized Population [J].
Fang, Yi ;
Ding, Xiaoqiang ;
Zhong, Yihong ;
Zou, Jianzhou ;
Teng, Jie ;
Tang, Ying ;
Lin, Jing ;
Lin, Pan .
BLOOD PURIFICATION, 2010, 30 (02) :120-126
[10]   Role of CXC chemokine receptor 3 pathway in renal ischemic injury [J].
Fiorina, Paolo ;
Ansari, Mohammed Javeed ;
Jurewicz, Mollie ;
Barry, Mark ;
Ricchiuti, Vincent ;
Smith, Rex Neal ;
Shea, Susan ;
Means, Terry K. ;
Auchincloss, Hugh, Jr. ;
Luster, Andrew D. ;
Sayegh, Mohamed H. ;
Abdi, Reza .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (03) :716-723