Vol 49 No. 4: 338-348 [PDF] [Full Text]
Therapeutic potential of mesenchymal stem cells in acute kidney injury is affected by administration timing
Xiaoyan Liu1,2,3, Jieru Cai1,3, Xiaoyan Jiao1,3, Xiaofang Yu1,3,*, and Xiaoqiang Ding1,3,4,*

1Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China,
2Department of nephrology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China,
3Shanghai Institute of Kidney Disease and Dialysis, Shanghai 200032, China, and
4Shanghai Key Laboratory of Kidney disease and Blood Purification, Shanghai 200032, China

Abstract  Mesenchymal stem cell (MSC) transplantation is a promising therapy for acute kidney injury; however, the efficacy is limited due to poor survival after transplantation. In this study, we investigated how MSC transplantation timing affected the survival and therapeutic potential of MSCs in the kidney ischemiaCreperfusion (I/R) injury model. After kidney I/R injury, the inflammatory process and tissue damage were characterized over 1 week post-I/R, we found that inflammation peaked at 12C24 h post-I/R (h.p.i.), and urine neutrophil gelatinase-associated lipocalin (NGAL) measurements correlated highly with measures of inflammation. We cultured MSCs with supernatants from I/R injured kidney tissue homogenates collected at different time points and found that kidney homogenates from 12 and 24 h.p.i. were most toxic to MSCs, whereas homogenates from 1 h.p.i. were not as cytotoxic as those from 12 and 24 h.p.i. Compared with MSCs administered at 12, or 24 h.p.i., cells administered immediately after ischemia or 1 h.p.i. yielded the highest renoprotective and anti-inflammatory effects. Our findings indicate that MSC treatment for acute kidney injury is most effective when applied prior to the development of a potent inflammatory microenvironment, and urine NGAL may be helpful for detecting inflammation and selecting MSC transplantation timing in I/R kidney injury.


Keywords   acute kidney injury, inflammation, ischemia/reperfusion, mesenchymal stem cells, timing, neutrophil gelatinase-associated lipocalin


Received   2016-12-16  


Funding  This work was supported by the grants from National Natural Science Funds of China (Nos. 81570600 and 81430015) and Shanghai Young Physician Training Program (No. 20141089).


* Correspondence address  Tel: +86-13918427113; E-mail: yu.xiaofang@zs-hospital.sh.cn (X.Y.)/Tel: +86-13601968215;Fax: +86-21-64041990-3263; E-mail: ding.xiaoqiang@zs-hospital.sh.cn (X.D.)

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