Stem Cell Based Preclinical Drug Development and Toxicity Prediction

Abstract

: Stem cell based toxicity prediction plays very important role in the development of drug. Unexpected adverse effects of the drugs during clinical trials are a major reason for termination or withdrawal of drugs. Methods for predicting toxicity employ in vitro as well as in vivo models, however, the major drawback seen in the data derived from these animal models is lack of extrapolation, owing to interspecies variations. Due to these limitations, researchers have been striving to develop more robust drug screening platforms based on stem cells. The application of stem cells based toxicity testing has opened up robust methods to study the impact of new chemical entities on not only specific cell types, but also organs. Pluripotent stem cells, as well as cells derived from them, can be evaluated for modulation of cell function in response to drugs. Moreover, the combination of state-of-the -art techniques such as tissue engineering and microfluidics to fabricate organ-on-a-chip, has led to assays which are amenable to high throughput screening to understand the adverse and toxic effects of chemicals and drugs. This review summarizes the important aspects of the establishment of the embryonic stem cell test (EST), use of stem cells, pluripotent, induced pluripotent stem cells and organoids for toxicity prediction and drug development.