Though it is difficult to predict the side effects of a drug on a person in advance, scientists of Singapore have used patients’ stem cells to test side effects of drugs.
Scientists from the Institute of Bioengineering and Nanotechnology (IBN) of A*STAR (The Agency for Science, Technology and Research) and the National Cancer Centre Singapore (NCCS) have demonstrated a promising approach to screen for severe side effects by first testing the drug on stem cells made from the patient’s blood.
Speaking about the side effects of drugs, Professor Jackie Y. Ying, Executive Director at IBN, said “Adverse side effects from drugs are a major clinical concern, which could and should be preventable. Knowing whether an individual is susceptible to a particular medicine will improve healthcare and treatment outcome. We are confident that our personalized stem cell technology will be of significant clinical value.”
This research project was led by Dr Min-Han Tan, Team Leader and Principal Research Scientist and Professor Hanry Yu, Group Leader, at IBN. NCCS recruited the kidney cancer patients and provided clinical data and analysis.
In the test, scientists of Singapore used induced pluripotent stem cells – which can transform into any type of cells in the body – to create liver cells from the blood of five kidney cancer patients. Their liver cells were then exposed to the cancer drug pazopanib, which can cause liver damage. Three of the patients 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. Further, using these stem cells, the researchers were able to analyze how the drug caused liver damage, which was previously unknown to doctors. This study was published in Scientific Reports.
Dr Min-Han Tan said “Our hypothesis was that liver cells made from the individual’s blood might show similar sensitivity or resistance to pazopanib. 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.”
This clinical validation in patients suggests that it would be possible to screen personalized stem cells, comprising a range of liver, lung, kidney and heart cells, to predict whether the patient would get side effects from taking a particular drug.
Prof Hanry Yu added, “Liver toxicity caused by therapeutics can lead to organ damage and chronic disease. 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.”
Excited about this discovery, Dr Ravindran Kanesvaran, Consultant at NCCS, said, “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.”
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.
