Singapore researchers develop 1st animal-free screening platforms to predict toxic kidney injury

Researchers from the Institute of Bioengineering and Nanotechnology (IBN) in Singapore have developed the first animal-free screening platforms capable of predicting the toxic effects of compounds on the human kidney accurately, the Agency for Science, Technology and Research (A* STAR) said in a press release on Friday.

The latest technological advancement involves the use of human induced pluripotent stem cells (iPSCs) in their renal screening platform. To realize this breakthrough, scientists have developed an effective way of producing human renal cells from iPSCs, and have combined this with machine learning methods that improved the automated and accurate prediction of nephrotoxicity, A*STAR said, adding that the new platform also correctly identifies injury mechanisms, which can help to advance understanding of the tested compounds.

"Our new kidney screening platforms will be very useful for many industries that require a reliable tool for evaluating the safety of compounds and ingredients. For example, the chemical and pharmaceutical industries produce a large number of new compounds that need to be screened and tested. Likewise, there is a demand in the food and consumer care industries for efficient lab tools to predict the safety of novel ingredients in their products," said IBN Executive Director Professor Jackie Y. Ying.

Due to their role in the elimination of drugs and other foreign compounds from the body, the kidneys are a main target for compound-induced toxicity. Many widely used chemicals and drugs, such as anti-cancer drugs, antibiotics and immunosuppressants, are harmful to the kidneys and may cause organ damage or failure.

Approximately 20 percent of hospital and community acquired cases of acute kidney injury were caused by such compounds, A*STAR explained, stating that a drug's toxic effect on the kidney would typically be discovered only in the late stages of drug development or even after the product has been marketed. " Therefore, the ability to determine a new drug's toxicity earlier in the development phase would be of great interest to pharmaceutical companies, which could spend approximately 1 billion to 2 billion U.S. dollars on average to develop a new drug, " it said.

Moreover, there're challenges in using animal models to predict the nephrotoxicity of a new compound, including high costs, unreliable results, as well as ethical issues, and validated and accepted animal-free methods are currently not available in the market.

Over the past three and a half years, a research team led by IBN Team Leader and Principal Research Scientist Daniele Zink has developed the first and only cell-based renal screening platforms that can predict nephrotoxicity with high accuracy. After repeated experiments, the researchers worked on an approach using human iPSCs as it can be generated from cells that are easily available in any person. Such models would help to provide a better understanding of renal disease and facilitate the development of personalized therapies and drugs.

"We have developed the fastest and most efficient protocol for generating kidney cells from induced pluripotent stem cells. Within eight days, it yielded highly pure kidney cells that were suitable for compound screening...We hope that our work will contribute to the development of safer products in future," according to Zink.

The researchers plan to work with industrial partners to further validate and apply their renal screening platforms. Endi