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 12-24h post-I/R (h.p.i.),and urine neutrophil gelatinase-associated lipocalin (NGAL) measurements correlated highly with measures of inflammation.We cultured MSCs with supeatants from I/R injured kidney tissue homogenates collected at different time points and found that kidney homogenates from 12 and 24h.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.