Scientists at Singapore’s Institute of Bioengineering and Nanotechnology have created a non-animal drug screening method that uses stem cell-derived human kidney cells to predict the toxicity of drugs and other chemicals. The method improves on the reliability and availability of earlier stem cell models, promises to reduce the costs and time it takes to test and develop new drugs, and could eventually eliminate certain animal tests.
Because of their role in filtering blood, the kidneys are especially vulnerable to any toxic effects of drugs and other substances that pass through them, but predicting the renal toxicity of such substances has been difficult. As the authors write in their article in Scientific Reports, “Typically, compound nephrotoxicity is only detected during late stages of drug development, which is associated with high costs for the pharmaceutical industry. Animal models have limited predictivity and the development of renal in vitro models with high predictivity has been challenging.”
Using primary human kidney cells in toxicity tests is difficult, as well, due to high variability between donors, and difficulties keeping the cells fully functional during tests. For these reasons, generating a reliable supply of kidney cells from stem cells is preferable. Previous human kidney cell models (including one published by the authors) were produced from human embryonic stems cells (hESCs), which are difficult to access and which raise ethical concerns. This new method instead uses induced pluripotent stem cells (iPSCs) created from more readily available cells, such as human skin cells. iPSCs are genetically “reprogrammed” to an early developmental state, from which they can be coaxed into other kinds of cells. The team’s method produces usable kidney cells within 8 days – much faster than previous stem cell models, as well.
To learn more about using stem cells in toxicity testing, read the “primer” on AltTox.org.