A Stanford study adds a powerful example to our growing list of diseases that have yielded their secrets to iPS-type stem cells grown in a dish. These “disease-in-a-dish” models have become one of the most rapidly growing areas of stem cell science. But this time they did not start with skin from a patient with a genetic disease and see how that genetic defect manifests in cells in a dish. Instead they started with normal tissue and looked at how the resulting cells reacted to viral infection.
They were looking at a nasty heart infection called viral myocarditis, which can begin to cause damage to heart muscle within hours and often leads to death. Existing antiviral drugs have only a modest impact on reducing these infections. So even though there is an urgent need to find better drugs, animal models have not proven very useful and there is no ready supply of human heart tissue for lab study.
To create a ready supply of human heart tissue Joseph Wu’s CIRM-funded team at Stanford started with skin samples from three healthy donors, reprogrammed them into iPS cells and then matured those into heart muscle tissue. Then they took one of the main culprits of this infection, coxsackievirus, and labeled it with a fluorescent marker so they could track its activity in the heart cells.
They were able to verify that the virus infected the cells in a dish just as they do in normal heart tissue. And when they tried treating the cells with four existing antiviral drugs they saw the same modest decrease in the rate of infected cells seen in patients. For one of the drugs that had been shown to cause some heart toxicity, they also saw some damage to the cells in the dish.
They propose that their model can now be used to screen thousands of compounds for potentially more effective and safer drugs. They published their results in Circulation Research July 15.