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12 Mar 2015

Human Stem Cells to Track the Side Effects of New Drugs

According to the scientists at Imperial College London, there is a new test that uses a combination of endothelial cells developed from adult stem cells and WBCs from the same donor to detect severe side effects of new drugs in humans during clinical trial.

In 2006, around 6 healthy young men who volunteered for the TGN1412 drug trial were admitted in intensive care for multiple organ failure due to the catastrophic side effect of the drug. The TGN1412 drug caused a severe inflammatory reaction known as cytokine storm which was specific only to humans. The cytokine storm created concerns regarding the usage of biological materials like antibodies in human trials. As the drugs are specific to humans, severe inflammatory reactions are not observed in animal studies, making it difficult to detect or avoid in human trials.

The cytokine storm depends on the interaction of blood cells and endothelial cells to manifest the side effects. The endothelial cells are present on the lining of the blood vessels, found deep within the body. For research studies, endothelial cells are usually grown from the tissue removed in surgery, post mortem or from umbilical cord vein after birth. Due to this, current research studies use endothelial cells from one donor and white blood cells from another donor. When cells from 2 different donors are used, they cause immune reaction as the system is primed for inflammation even before adding the drug. Such a condition will exhibit faulty result even for a safe drug.

To overcome this hindrance, the scientists at Imperial College London isolated stem cells from the blood of a volunteer and used them to grow endothelial stem cells in the lab. Along with the lab grown endothelial cells, they used white blood cells from the same volunteer to recreate a system similar to human blood vessels with all the unique conditions. To test the system, scientists added TGN1412 drug which initiated a cytokine storm, as would happen in the human body. The strategy of using endothelial cells and blood cells from a single donor created more reliable test models for new drug trials. The researchers of this study believe that such a test can prevent any other future disaster like the TGN1412 trial. The lead author of the study, Daniel Reed mentioned that this technology can be used for personalized medicine to test if a particular drug is safe and effective for individuals based on their immune response.



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