Therapeutic potential of mesenchymal stem cells in acute kidney injury is affected by administration timing.
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 ischemia-reperfusion (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 12-24 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.
Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Department of nephrology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China.|Shanghai Institute of Kidney Disease and Dialysis, Shanghai 200032, China.
Xiaoyan
X
Liu
Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Shanghai Institute of Kidney Disease and Dialysis, Shanghai 200032, China.
Jieru
J
Cai
Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Shanghai Institute of Kidney Disease and Dialysis, Shanghai 200032, China.
Xiaoyan
X
Jiao
Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Shanghai Institute of Kidney Disease and Dialysis, Shanghai 200032, China.
Xiaofang
X
Yu
Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.|Shanghai Institute of Kidney Disease and Dialysis, Shanghai 200032, China.|Shanghai Key Laboratory of Kidney disease and Blood Purification, Shanghai 200032, China.
Xiaoqiang
X
Ding
D058186:Acute Kidney Injury / Q000276:immunology / Q000628:therapy* / Q000652:urine; D000818:Animals; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology / Q000652:urine; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2 / Q000652:urine; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology / Q000628:therapy* / Q000652:urine; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D016207:Cytokines; D018836:Inflammation Mediators; C489506:LCN2 protein, human; D000071068:Lipocalin-2
acute kidney injury; inflammation; ischemia/reperfusion; mesenchymal stem cells; neutrophil gelatinase-associated lipocalin; timing