Growing resilient heart cells for therapy and drug discovery
Graduate Education Grant Recipient: Matthew Wheelwright
Faculty Sponsor: Joseph M. Metzger
Grant Period: 2015-2016
Site: Integrative Biology & Physiology | University of Minnesota
Recent technology has made it possible to transform human skin cells into stem cells under laboratory conditions and transform the stem cells into heart muscle cells. This process is only a few years old, and little is currently known about the resulting heart cells. For example, researchers do not know how much force and electrical activity the artificially-developed heart cells have when compared to regular heart cells. This makes it difficult to use the cells for research.
Most of the research currently performed on drugs to improve heart performance is done with animal heart cells or with cells that are expressing proteins that one might find in human cells. The results may be difficult to apply to humans, though, as the tests only reflect effectiveness in animals. This makes it difficult to establish how drugs will perform in people, and it slows the process of testing and discovering effective new drugs.
Another problem is that previous attempts to inject heart cells grown outside the body into a functioning heart resulted in most of the new cells dying. Given the fact that the heart is a stressful and low-oxygen, or hypoxic, environment, it is possible that the laboratory-grown cells are not resilient enough to withstand these conditions.
This project will perform additional research on lab-grown heart cells and discover ways to accurately measure their performance. Because these heart cells do not seem to perform as well as regular ones, researchers are also planning to modify their genome so the cells can better withstand the stressful environment of a human heart. Researchers will attempt to identify and activate a gene that will make the performance of laboratory cells equivalent to regular heart cells and improve their potential for use in therapy and research.
Having an abundant supply of strong human heart cells available would create therapeutic potential for millions of people who have suffered a heart attack or have heart disease to undergo effective treatments. Transplanted heart cells could help strengthen the heart's contractions by providing the force themselves or encouraging existing heart cells to perform more work, whereby helping the heart repair itself.
Another benefit to this research is that it can reduce the need to use animals for drug research. If scientists can grow an unlimited supply of heart cells that perform synonymously with cells in a human heart, then they can test new drugs and therapies to develop effective solutions to the problems of heart disease and heart failure in relatively more ethical ways.
The research will also add to the body of knowledge about how to genetically alter laboratory cells to perform in hypoxic environments. Many other types of cells, including cancer cells, are also exposed to low-oxygen environments. Therefore, this research could help others develop cells for use in cancer research and treatment.
Matthew Wheelwright is a graduate student in the Medical Scientist Training Program at the University of Minnesota. He earned his B.S. in neuroscience from the University of California, Los Angeles in 2010. He was awarded the Warwick MD/PhD Student Fellowship for the 2013-14 school year, which has allowed him to focus more specifically into his main area of interest, molecular cardiology.