A cell imaging-based screening approach predicts toxic effects of chemicals on the human kidney

June 2, 2016, Agency for Science, Technology and Research (A*STAR), Singapore
A cell imaging-based screening approach predicts toxic effects of chemicals on the human kidney
Human renal proximal tubule cells treated with Dexamethasone (non toxic, left) and Bismuth Oxide (toxic, right). Credit: A*STAR Bioinformatics Institute and the Institute of Bioengineering and Nanotechnology

Thousands of new drug candidates and compounds must be tested every year to ensure their safety for humans, and toxicity is one of the main reasons for their failure. Animal models are widely used for this purpose, but they offer low efficiency. A*STAR researchers have now combined cell biology and computational expertise to find alternative, animal-free, toxicity testing methods.

Daniele Zink and Lit-Hsin Loo from the A*STAR Institute of Bioengineering and Nanotechnology and Bioinformatics Institute, respectively, are co-lead authors of a study that describes an approach for screening large numbers of compounds for toxic effects in human renal proximal tubular cells (PTCs). These cells have key roles in and act to eliminate drugs and chemicals from the body. PTCs are often damaged in patients with compound-induced kidney injury, but little is known about the early mechanisms and markers of injury. To predict compound , the researchers treated laboratory-grown PTCs with a range of reference chemicals and developed an automated procedure to identify the first signs of damage.

Using machine-learning techniques to automatically analyse 129 image-based cell features, the researchers were able to predict PTC toxicity in humans with more than 80 per cent accuracy, irrespective of any knowledge of the compounds' chemical structure. "We were surprised that it worked so well," says Zink. "The screening results tell us, in an unbiased way, a lot about the cellular injury occurring in the samples," she adds.

The results indicate that most PTC-toxic compounds cause damage to the cells' DNA, despite the fact that many of them have not been found to directly target DNA. "We suspect that DNA damage may be a common response to different PTC injury-causing agents," explains Loo.

This animal-free model to predict kidney toxicity in humans will be especially useful during the initial stages of product development, where the safety of potential chemical ingredients must be evaluated. The researchers are now collaborating with the US Environmental Protection Agency to predict the kidney toxicity of hundreds of environmental chemicals, and they are developing a similar approach to predict liver- and lung-specific toxicities.

The next step will involve obtaining regulatory approval, which as Zink remarks "would be important for putting Singapore on the map as a global player in the rapidly growing in vitro safety testing market."

Explore further: Kidney cells made from reprogrammed stem cells lead scientists to an accurate way to screen for toxic compounds

More information: Ran Su et al. High-throughput imaging-based nephrotoxicity prediction for xenobiotics with diverse chemical structures, Archives of Toxicology (2015). DOI: 10.1007/s00204-015-1638-y

Related Stories

Kidney cells made from reprogrammed stem cells lead scientists to an accurate way to screen for toxic compounds

November 18, 2015
A platform that could help pharmaceutical, chemical and food companies screen for safe compounds for kidneys has been set up by A*STAR scientists, who have created the fastest and most efficient protocol for coaxing stem ...

Researchers develop first animal-free screening platforms to predict toxic kidney injury

October 12, 2015
Researchers from the Institute of Bioengineering and Nanotechnology (IBN) have developed the first animal-free screening platforms capable of predicting the toxic effects of compounds on the human kidney accurately. Their ...

Cell-based tests promise respite for lab animals: study

January 26, 2016
Scientists in the United States said Tuesday they were developing a faster, more efficient way of gauging the toxicity of chemicals, which may reduce the need for animal testing.

In lab studies, hydroxyethyl starch has direct harmful effects on kidney cells

July 11, 2014
The increased risk of kidney injury related to the use of hydroxyethyl starch (HES) in resuscitation fluids reflects the mass of HES molecules, according to a report in Anesthesia & Analgesia, official journal of the International ...

Unlimited source of human kidney cells: Applications include in vitro toxicology, disease models, regenerative medicine

February 21, 2013
Researchers at the Institute of Bioengineering and Nanotechnology (IBN) have successfully generated human kidney cells from human embryonic stem cells in vitro. Specifically, they produced the renal cells under artificial ...

Recommended for you

New inflammation inhibitor discovered

November 16, 2018
A multidisciplinary team of researchers led from Karolinska Institutet in Sweden have developed an anti-inflammatory drug molecule with a new mechanism of action. By inhibiting a certain protein, the researchers were able ...

Gut hormone and brown fat interact to tell the brain it's time to stop eating

November 15, 2018
Researchers from Germany and Finland have shown that so-called "brown fat" interacts with the gut hormone secretin in mice to relay nutritional signals about fullness to the brain during a meal. The study, appearing November ...

Brain, muscle cells found lurking in kidney organoids grown in lab

November 15, 2018
Scientists hoping to develop better treatments for kidney disease have turned their attention to growing clusters of kidney cells in the lab. One day, so-called organoids—grown from human stem cells—may help repair damaged ...

How the Tasmanian devil inspired researchers to create 'safe cell' therapies

November 15, 2018
A contagious facial cancer that has ravaged Tasmanian devils in southern Australia isn't the first place one would look to find the key to advancing cell therapies in humans.

Researchers discover important connection between cells in the liver

November 15, 2018
University of Minnesota Medical School researchers have made a discovery which could lead to a new way of thinking about how disease pathogenesis in the liver is regulated, which is important for understanding the condition ...

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Jun 02, 2016
Interesting in this article

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.