Acute Kidney Injury Models: Focus on the Therapeutic Effects of Stem Cell in Preclinical Approach

초록

Stem cell-based therapy is under intensive investigation to treat acute renal failure (ARF). The purpose of this study was to evaluate available ARF models, and suggest a model appropriate to therapeutic evaluation of the stem cells in preclinical approach by determining the optimum concentration of nephrotoxic agents and duration of ischemia induction. Three different types of available acute kidney injury (AKI) animal models were analyzed using rats: Cisplatin (saline, 5 and 7.5 mg/kg, IP) or glycerol (saline, 8 and 10 ml/kg, IM)-induced nephrotoxicity as toxic models and ischemia-induced (sham, 35 and 45 minutes) nephropathy as an ischemic model. The relevance and applicability to investigate especially the regenerative ability of stem cells were evaluated regarding morphology, renal function and survival at this time point. In the point of renal function, 10 ml glycerol/kg and 7.5 mg cisplatin/kg model in toxic models and 45 min model in ischemia models showed significant decrease for the longer observation time compared to 8 ml glycerol/kg, 5 mg cisplatin/kg and the 35 min ischemia models, respectively. All groups were observed no mortality except 45 min-ischemia model with 50% survival. Histological significant alterations including cast formation in the tubular lumen, tubular necrosis and apoptosis were revealed on the second day in either ischemiaor glycerol-induced models, and on day 5 in cisplatin-induced models. The results indicate that ischemia 35 min-,cisplatin 7.5 mg/kg- and glycerol 10 ml/kg-induced AKI would be ideal animal models to monitor a outcome parameter related to the therapeutic effects on renal function with noninvasive techniques in the same animal at multiple time points. Our findings also suggest that the best time points for the functional or histological interpretation of renal will be on day 2 in both glycerol- and ischemia-induced AKI models and on day 5 in cisplatin-induced AKI.

키워드