Utilizing patient-specific stem cells for heart disease modeling
Graduate Scholar: Saranya P. Wyles
Faculty Sponsor: Timothy J. Nelson
Grant Period: 2015-2016
Site: Mayo Graduate School | Mayo Clinic
Heart disease is one of the leading causes of death in the United States. Approximately 750,000 Americans currently live with dilated cardiomyopathy (DCM), where the heart muscle stretches in one or more chambers, enlarging (dilating) the open area of the heart in the process. As all four chambers dilate, the cardiac muscle works harder to pump blood, an effort that eventually leads to heart failure. One third of the patients with DCM inherited the disease.
While medical experts have made great strides in treating people with DCM, the current standard of therapy is not guided by patient-specific factors like disease severity or what kind of genetic mutation caused the disease.
Saranya P. Wyles’ project aims both to improve the medical community’s understanding of how DCM develops and to use regenerative medicine to individualize cardiovascular disease care. To do this, Wyles is developing and analyzing heart cells grown in a laboratory.
First, a small sample of the heart patient’s skin is collected. Then she converts the skin cells back into a stem cell state using a Nobel-prize winning technology called nuclear reprogramming. Finally, these stem cells, known as induced pluripotent stem cells, are grown into living heart cells. Once these patient-specific heart cells develop a pulse, they are exposed to drugs that increase the heart rate, such as norepinephrine and isoproterenol, and then treated with different heart failure therapies, such as beta blockers and calcium channel blockers.
Although all patients with DCM are currently treated with beta blockers, Wyles found that calcium channel blockers were more effective in regulating the stress response in the heart cells from DCM patients with a specific genetic mutation.
Wyles is currently studying patient-specific heart cells in the lab to identify at which point in their development the heart cells diverge from natural development and become diseased cells.
By growing patient-specific heart cells in a laboratory environment using stem cell technology, medical professionals will be able to customize treatments for individuals. Instead of all patients with DCM universally receiving the same treatment for heart failure, for example, doctors will be able to grow heart cells from their patients’ skin cells and test various treatments on these new cells to tailor the most effective therapy for each individual. This is especially relevant for the pediatric population where clinical trials are limited.
Wyles’s work improving this technology for DCM helps make this model of individualized medicine available for other diseases as well.
Saranya P. Wyles is enrolled in Mayo Clinic’s Center for Clinical and Translational Sciences (CCaTS) track of the MD-PhD program, where she is gaining the valuable experience of running collaborative and interdisciplinary teams conducting bench-to-bedside research. Wyles earned her BA in Neuroscience from Columbia University’s Barnard College in New York City. She has over a decade of experience in cardiology and stem cell research in laboratories at the Mt. Sinai School of Medicine, Liverpool John Moores University in the UK, Magna Graecia University in Italy, and the Harvard Stem Cell Institute. After completing her education at Mayo Clinic, she would like to become a physician-scientist in an academic practice.