New animal-free screening platforms for kidney-toxic effects

SINGAPORE — Researchers in Singapore have developed the first animal-free screening platforms that can accurately predict the toxic effects of compounds on the human kidney.

Instead of testing on animals, scientists make use of human renal cells, produced from human-induced pluripotent stem cells, together with machine-learning methods.

“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,” said executive director Professor Jackie Ying of the Institute of Bioengineering and Nanotechnology (IBN), where the cell-based screening method was developed. Professor Ying cited examples such as the chemical and pharmaceutical industries, and food industry.

The new platform, which can also identify how the damage occurs to the kidneys, was announced by the Agency for Science, Technology and Research (A*STAR) this month. IBN is a research institute at A*STAR.

A*STAR noted that kidneys are the main target for compound-induced toxicity because of their role in eliminating drugs and other foreign compounds from the body. It noted that 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. The toxic effect on a kidney is usually discovered in the late stages of drug development or after a 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 US$1 billion (S$1.4 billion) to US$2 billion on average to develop a new drug,” said A*STAR.

Using animal models to predict the toxic effect on kidneys faces challenges such as the long time required, high costs, unreliable results and ethical issues. There is currently no validated and accepted animal-free method.

The screening platform took more than three-and-a-half years to develop. Earlier versions tried using human primary renal proximal tubular cells or similar cells derived from human embryonic stem cells, but faced various problems, including limited availability and ethical and legal concerns.

The IBN team found a way to produce suitable kidney cells from human-induced pluripotent stem cells (iPSCs) — adult cells that are genetically reprogrammed to an embryonic, stem-cell-like state — within eight days. They worked with the Bioinformatics Institute to develop data analysis and machine-learning methods to predict toxic effects on a kidney.

“As iPSCs can be generated from cells that are easily available in any person … they could also be used to develop patient- and disease-specific models. Such models would help to provide a better understanding of renal disease and facilitate the development of personalised therapies and drugs,” said A*STAR.

Animal-free screening methods are mandatory for cosmetic firms selling their products in the EU, India and Israel. The researchers plan to work with industrial partners to validate and apply their renal screening platforms.


Date: 24/10/2015