Stem Cells Used For Personalized Liver Drug Screening

Testing cancer drugs on liver cells made from the stem cells of patients could help reduce the incidence of adverse drug responses, researchers say.

AsianScientist (Mar. 7, 2017) – Researchers from Singapore have developed a personalized method to screen for severe side effects by using stem cells from the patient’s own blood. Their findings have been published in Scientific Reports.

In Singapore, approximately eight percent of all hospital admissions are caused by adverse drug reactions and these patients typically require a longer hospitalization stay. In Europe, side effects from medications cause 197,000 deaths annually.

“Liver toxicity caused by therapeutics can lead to organ damage and chronic disease,” explained study co-author Professor Hanry Yu from the Singapore’s Agency for Science, Technology and Research (A*STAR) Institute of Bioengineering and Nanotechnology.

“Currently, new drugs are tested for toxicity using generic liver cells, which cannot model patient-specific reaction. By personalizing liver cells from the blood of individual patients, we can help doctors to prescribe safer and more effective therapies.”

To test how individual kidney cancer patients would react to a given drug, the team of researchers led by Dr. Tan Min-Han from the National Cancer Centre Singapore (NCCS) created induced pluripotent stem (iPS) cells from the blood of each patient. The iPS cells were then differentiated into liver cells and exposed to the cancer drug pazopanib, which can cause liver damage. Three of the five patients studied were known to react badly to pazopanib, while two of them did not have any side effects.

The results showed that each patient’s newly created liver cells exhibited the same sensitivity to the drug when compared with their post-treatment data from liver biopsies. Furthermore, the researchers were able to analyze how the drug caused liver damage, which was previously not known.

“This study is the first proof-of-concept that our approach can predict drug-induced liver damage for an individual. Importantly, we were able to figure out how the drug works from the way they react to the liver cells, which was unknown to doctors, even after many years of using this drug,” said Tan.

This clinical validation in patients suggests that it would be possible to predict whether a patient would get side effects from taking a particular drug using similar stem cell-derived personalized screens.

“We are very excited that this study demonstrates an approach that could transform how drug toxicities are evaluated. It also sheds light on the mechanism of a particular side effect of pazopanib, which may lead to ways to overcome it. We are already planning formal clinical trials on this,” said study co-author Dr. Ravindran Kanesvaran, consultant at NCCS.

The research team will conduct further studies on drugs that affect other types of organs, and hope to work with industry partners to commercialize this technology.

The article can be found at: Choudhury et al. (2017) Patient-Specific Hepatocyte-Like Cells Derived from Induced Pluripotent Stem Cells Model Pazopanib-Mediated Hepatotoxicity.


Source: A*STAR; Photo: Shutterstock.
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