Gel Entrapment Culture Of Renal Tubular Epithelial Cell And Hepatocyte For Evaluation Of Drug Toxicity

During drug development, the application of cell culture model for drug toxicity screening could facilitate to eliminate drug candidates with high toxicity, thus shorten the development phase and reduce the cost. To date, the monolayer culture model is the most commonly used in vitro model. But the toxicity of drugs in vivo could not always be accurately reflected due to its poor maintainance of the organ specific function. Therefore, according to the established model for screening drug hepatotoxicity in vitro in our lab, this study employed the gel entrapment model for renal tubular epithelial cell culture, hoping to replace the existing monolayer culture model for drug toxicity evaluation in vitro.This study covers three parts as following.Firstly, the gel entrapment model was employed for primary renal tubular epithelial cell culture. It was demonstrated that gel entrapped renal tubular epithelial cell self-assemblly formed tubule-like structure. On the other hand, the cellular differentiation functions were better maintained in gel entrapment model, compared with monolayer culture.Secondly, four model drugs, including gentamicin, azathioprine, cyclosporin A and cisplatin, were used to evaluate the feasibility of applying gel entrapped renal tubular epithelial cells and hepatocytes for drug nephrotoxicity and hepatotoxicity screening, respectively. Comapred with the toxic response in monolayer culture model, gel entrapment culture model could better reflect the drug toxicity in vivo.Finally, the organ specific drug toxicity was evaluated via comparing differetial toxic response in renal tubular epithelial cells and hepatocytes cultured in both models. It was found that gel entrapment culture model could better reflect the organ specific drug toxicity in vivo.In conclusion, gel entrapment model could reflect the drug nephrotoxicitry and organ specific drug toxicity in vivo. Thus, the model has great potential in screening protective agents for nephrotoxic drugs. And it could also be used in tissue engineering research.