A Faster, Less Expensive Way to Create Heart Tissue for Testing

Researchers from the University of California, San Francisco (UCSF) have designed new stem cell-based procedure that can make three-dimensional heart tissue that can serve as a model system for drug testing and particular diseases. This new technique reduces the number of cells required to make a mini-three-dimensional heart tissue patch. Thus, this procedure can produce a cheaper, more efficient system that is also easier to set up and use.

Bruce Conklin and his colleagues published their results in the internationally acclaimed Proceedings of the National Academy of Sciences USA (DOI:10.1073/pnas.1519395113). This bioengineered microscale heart tissue provides the means for heart researchers to study heart cells in their proper context.

To design their protocol, Conklin and his colleagues used induced pluripotent stem cells (iPSCs), which are made from the mature, adult cells of patients by means of genetic engineering cell culture techniques.  Induced pluripotent stem cells can be differentiated into heart muscle cells, but the cells made iPSCs tend to be rather immature.  Furthermore, experiments with these immature heart muscle cells often requires large quantities of cells that take time and expense to cultivate.

Conklin’s microheart muscles are stretched into highly organized clusters that drive their further differentiation.  After the iPSCs are differentiated into heart muscle cells, they are grown in dog bone-shaped culture dishes that spreads the cells out and forces them to organize properly. This physical arrangement drive their differentiation.  Within a couple of days, the miniheart tissues structurally and functionally resemble heart muscle.  These more mature heart muscles cells provide more realistic information about how a particular experimental drug might affect the heart.  These microscale hearts require up to 1000-fold fewer cells, which allows for more tests, better data, and less hassle all for less expense.

As a demonstration of the maturity of the microscale heart tissue system, Conklin and his group treated their cells with a drug called verapamil.  Verapamil is a member of the “calcium channel blocker” family of drugs.  It inhibits the so-called “L-type” calcium channels, which lowers the delayed rectifier current potassium channel.  The upshot is that heart blood vessels dilate, which send more blood and oxygen to heart muscle, and the activity of the heart muscle is slowed.  However, fetal heart muscle cells are impaired by verapamil, but adult cells, while slowed, are not impaired.  Conklin’s minihearts showed a more adult response to verapamil, which strongly suggests that the cells in this structure are more adult than they are fetal.

The Gladstone Institute researcher, Bruce Conklin, and senior author of this article, said: “The beauty of this technique is that it is very easy and robust, but it still allows you to create three-dimensional miniature tissues that function like normal tissues.  Our research shows that you can create these complex tissues with a simple template that exploits the inherent properties of these cells to self-organize.  We think that the microheart muscle will provide a superior resource for conducting research and developing therapies for heart disease.”