A Symposium Session, Use of Stem Cells in Toxicity Testing—From Basic Research to Personalized Toxicology, was presented on Monday, March 24 at the 53rd Annual Meeting of the Society of Toxicology in Phoenix, Arizona. A summary of this session is provided below.
The need for more effective high-throughput tools for predicting human toxicity is growing more and more each day with the increased regulatory registration and risk assessment requirements. The field of research on induced pluripotent stem cells (iPSC) and their use in personalized therapy and toxicity testing is booming. Researchers have successfully developed iPSC-derived models for studying diseases of neural, cardiac, hepatic, and nephrotoxicity.
Nearly 15 years after James Thomson first derived human embryonic stem cells, his group has successfully turned peripheral blood cells into neural and cardiac cells while maintaining their in vivo morphology in 3D hydrogels. These cells, similar to three-mont-old fetal cells, have the correct organizational cellular structures complete with vascularization while maintaining normal function such as contractions in cardiomyocytes. What's more, these 3D structures provide a realistic model and are 80%–90% accurate for predicting human toxicity.
Chris Goldring from the University of Liverpool discussed the complexity of drawbacks surrounding poorly predictive models for Drug-Induced Liver Injury (DILI). Critical functions of the liver, such as metabolism and GSH detoxification, are often lost in human primary and immortalized cells. iPSC-derived hepatocytes, although promising, lack adequate P450 and GSH levels. However, a novel biomarker for DILI in iPSC-derived hepatocytes has been discovered, which correlates with in vivo findings. Also discussed was the development of iPSC-derived cardiomyocytes, which are much more accurate at predicting human cardiotoxicity than traditionally used CHO cells, and the complexity of predictive nephrotoxicity. The area of nephrotoxicity is of great importance although it does not receive much attention.
Overall, the experts demonstrated the huge advancements that have taken place in the field of iPSC despite the complex nature of human cells and tissues. It seems that each day we are getting closer and closer to achieving the goal of personalized therapy and toxicty testing!