If you suffer a heart attack, chances are, you’ll face a poor long-term prognosis. Fifteen percent of heart attack cases lead to congestive heart failure within just six months. Many patients with heart failure will eventually require heart transplants, but hearts available for transplant are in short supply. The majority of patients who experience heart failure will die within eight years.

Despite advanced therapeutic options, cardiovascular disease remains the leading cause of death worldwide. Stem cell therapy shows promise for healing damaged hearts and reducing the need for heart transplants, yet challenges remain for researchers as they work to develop clinical interventions.

UW Bioengineering alumnus and affiliate faculty member Patrick Hsieh is confronting these challenges by developing stem cell therapy strategies for treating cardiovascular disease and preventing heart failure. Dr. Hsieh’s research focuses on developing drug delivery and biomaterials that promote the survival, retention and integration of cardiac stem cells. Currently an associate research fellow at Academia Sinica in Taipei, Taiwan’s top research institution, Dr. Hsieh earned his Ph.D. from UW in 2003. Initially a cardiac surgeon, Dr. Hsieh combined his experience as a physician and education as a bioengineer at UW into a unique his multidisciplinary research approach.

In December 2014, the Taiwan Bio-Development Foundation recognized Dr. Hsieh’s contributions to the field of cardiac stem cell therapy and awarded him the country’s top biotechnology honor.

Discovering the body’s ability to heal the heart

The heart has limited capacity to regenerate and is vulnerable to damage. The heart largely consists of specialized muscle cells called cardiomyocytes. These cells help pump blood that carries oxygen and nutrients to the rest of the body. In a heart attack, blood flow to the heart is obstructed, blocking the cardiomyocytes’ oxygen supply. Cardiomyocytes cannot survive without oxygen, and up to a billion of these cells can die in typical heart attack. This cell death causes permanent damage to the heart, which can lead to heart failure.

Researchers have long investigated the role of stem cells in repairing cardiac damage. There has been particular interest in studying stem cell activity in the body and its role in promoting healing after injury.

Evidence suggests that bone marrow responds to inflammation signals produced by the body at time of injury. The bone marrow releases stem cells that enter the blood stream and travel to the site of damage to facilitate cell and tissue recovery. However, prior studies investigating how this mechanism responds to a heart attack have yielded conflicting results, even concluding that bone marrow-sourced stem cells circulating in the blood do not aid in cardiomyocyte regeneration.

Recent work published by Dr. Hsieh challenges previous findings. In a pivotal study published in Circulation Research, he demonstrated that circulating stem cells contribute to cardiomyocyte regeneration. He also found that inflammation at the time of heart attack plays an important role in promoting cardiac repair by signaling timely stem cell release.

Dr. Hsieh’s research group studied an animal model of two mice surgically connected to share blood circulation. After connecting the mice, they found that it took one week for the animals’ cross-circulation to stabilize. Once circulation between the mice was stable, the researchers examined circulating stem cell and cardiomyocyte activity before and after inducing a heart attack in the model.

They discovered that bone marrow-sourced stem cells responded to the heart attack by moving to the site of injury relatively quickly, within one week. There, not only did the stem cells transform to create new cardiomyocytes, but also helped protect the existing cells from cell death.

Dr. Hsieh’s work provides valuable insight into the healing and regenerative capacity of the human body following a heart attack. The potential for one’s own stem cells to help regenerate cardiomyocytes raises new possibilities for cardiovascular disease.

Ultimately, Dr. Hsieh hopes to translate his findings into clinical therapies that, when delivered soon after a heart attack, promote healing and prevent cardiac failure. “Although we still have a long way to go, we hope to develop drugs that strengthen the process of hematopoietic stem cells entering the heart so that patients can benefit from natural, endogenous cardiomyocyte regeneration,” he told the Taipei Times earlier this year.

A cardiac surgeon becomes a bioengineer

Despite being an accomplished researcher today, Dr. Hsieh’s didn’t start out as a bioengineer. As a young child, he enjoyed studying biology and chemistry, but as he grew older, his interest turned toward human anatomy, physiology and medicine. “I was attracted by the beauty of human nature,” he explains, and he found the ability of medicine to improve patients’ lives fascinating. To Dr. Hsieh, becoming a physician was an ideal way to integrate his passions for science and medicine into a productive career.

Dr. Hsieh entered Kaohsiung Medical College, the top medical school in Taiwan, in 1985, and specialized in cardiac surgery. “I chose my expertise based on my surgical talent and keen interest in cardiology,” he says. Moreover, he was impressed by the technology used in open-heart surgery.

Dr. Hsieh worked as a military doctor and general surgeon, eventually becoming a cardiac surgeon. As he established expertise in his field, he found himself frustrated by medicine’s limitations, from flaws in medical device technology to the lack of treatment options for incurable diseases. “I started to ask myself, can it be better?” he explains. “I had a gut feeling that a better and more efficient solution to these problems resided in biomedical research.”

Dr. Hsieh realized that by studying bioengineering, he could work toward solving challenges in health care. To him, UW was the ideal place to go. “It was one of the top in the world,” he explains, having outstanding faculty and a broad scope of research. “It covered almost all fields of bioengineering, which was not so common in the 1990s.”

Bioengineering Ph.D. study shapes Hsieh’s future in research

After being accepted to BioE’s Ph.D. program, Dr. Hsieh left his medical practice and moved to Seattle. He looked forward to the opportunity to gain a broader perspective of science and prepare for a career in research. “It is a choice that I have never regretted and a choice I proudly made.”

In BioE, he quickly learned the fundamentals of bioengineering practice and gained hands-on research experience in nanotechnology and stem cell biology. Working with mentors Cecilia Giachelli, now professor and the Hunter and Dorothy Simpson Endowed Chair of Bioengineering, and Alec Clowes, a UW professor of surgery and vascular surgeon, he studied how shear stress from blood flow regulated gene expression and tissue remodeling in vascular grafts using primate models of intimal hyperplasia, a healing response of a vessel to injury.

His research in BioE confirmed his interest in cardiovascular science, but Dr. Hsieh says that the foundational bioengineering knowledge and the relationships he developed during his study had a crucial impact upon his education. “The program definitely built my scientific network and broadened my knowledge horizons,” he says.

In BioE, Dr. Hsieh saw how diverse disciplines, ranging from tissue engineering and biomaterials to molecular biology and nanotechnology, integrate to produce biomedical innovation. He has translated this interdisciplinary approach to his research at Academia Sinica. His lab brings together researchers from stem cell biology, biochemistry, biophysics, materials science, clinical medicine and more.

Perhaps most important, Dr. Hsieh says, was how UW BioE helped him develop the characteristics essential for a successful research career. His mentors in BioE shaped not only his knowledge, but also his attitude towards the scientific process, he says. “I learned to question, to be tough to fight challenges and to discuss when there was a hurdle in my research,” he explains. Dr. Hsieh believes that these lessons influenced his learning philosophy and maximized his potential for success in his research career.