When a doctor gives you a medication you like to think that it’s safe, that it has been tested to make sure it will do you some good or, at the very least, won’t do you any harm. That’s particularly true when the patient is a pregnant woman. You hope the medication won’t harm her or her unborn child. Now scientists in Switzerland have found a new way to do that that is faster and easier than previous methods, and it uses cell cultures instead of animals.
Right now, drugs that are intended for use in pregnant women have to undergo some pretty rigorous testing before they are approved. This involves lots of tests in the lab, and then in animals such as rats and rabbits. It’s time consuming, costly, and not always accurate because animals never quite mimic what happens in people.
In the past researchers tested new medications in the lab on so-called “embryoid bodies”. These are three-dimensional clumps of cells developed from embryonic stem cells from mice. The problem is that even when tested in this way the cells don’t always reflect what happens to a medication as it passes through the body. For example, some medications can seem fine on the surface but after they pass through the liver can take on toxic qualities.
So, scientists at ETH Zurich in Basel, Switzerland, developed a better way to test for toxicity.
They took a cell-culture chip and created several compartments on it, in some they placed the embryoid bodies and in others they put microtissue samples from human livers. The different compartments were connected so that fluid flowed freely from the embryoid bodies to the liver and vice versa.
In a news release, Julia Boos, a lead author of the study, says this better reflects what happens to a medication exposed to a human metabolism.
“We’re the first to directly combine liver and embryonic cells in a body-on-a-chip approach. Metabolites created by the liver cells – including metabolites that are stable for just a few minutes – can thus act directly on the embryonic cells. In contrast to tests on mice, in our test, the substances are metabolised by human liver cells – in other words, just as they would be in the human body when the medication is administered.”
To see if this worked in practice the researchers tested their approach on the chemotherapy drug cyclophosphamide, which is turned into a toxic substance after passing through the liver.
They compared results from testing cyclophosphamide with the new liver/embryoid body method to the older method. They found the new approach was far more sensitive and determined that a 400 percent lower concentration of cyclophosphamide was enough to pose a toxic threat.
The team now hope to refine the test even further so it can one day, hopefully, be applied to drug development on a large scale.
Their findings are published in the journal Advanced Science