Singapore researchers develop cellular imaging platform for testing kidney toxicity

Researchers in Singapore have developed a highly efficient and accurate cellular imaging platform for predicting toxicity of compounds to the kidney, the Agency for Science, Technology and Research (A*STAR) said on Monday.

The approach, which combines cell culture, imaging and computational methods, could prove invaluable to companies from food, nutrition, cosmetics, consumer care, chemical and pharmaceutical industries by enabling them to predict the safety of their products while in development, the agency said in a statement.

Chemical compounds could injure the kidney and impair its function of eliminating waste from the body. About 20 percent of hospital or community acquired cases of acute kidney injury can be attributed to nephrotoxic drugs. Currently, there is no accurate method for screening large numbers of potentially nephrotoxic compounds with diverse chemical structures.

Over the past three years, researchers from A*STAR's Bioinformatics Institute (BII) and the Institute of Bioengineering and Nanotechnology (IBN) have worked together to develop cell-based screening methods to address the need, particularly as animal testing bans for cosmetics have been implemented in the EU, Norway, India and Israel, with many more countries expected to follow suit.

The researchers were able to develop the first and only cell-based renal screening platforms that can predict nephrotoxicity with high accuracy. Improving on this, the researchers have now developed an imaging-based method that can be used to test much larger numbers of compounds.

"By automatically analyzing more than 25,000 microscopy images of cells treated with different compounds, we were able to identify phenotypic signatures of kidney cells that can be used to predict the in vivo toxicity of compounds with diverse structures and mechanisms, with a validated accuracy of 80-90 percent." said Principal Investigator from BII who co-authored the study Lit-Hsin Loo.

In this study, more than 2 million individual cells were screened for their reactions to over 40 different chemical compounds, including industrial chemicals, antibiotics, antivirals, chemotherapy drugs and agricultural chemicals. The analysis was performed using an automated image analysis software called "cellXpress" that was developed by Dr. Loo's team at BII.

Team Leader and Principal Research Scientist from IBN Daniele Zink, who co-authored the paper, added that this novel software platform reduces the reliance on existing laborious and time-consuming methods currently available for testing of nephrotoxic compounds, enabling much faster predictions. Enditem