The grant, through the NIH's National Heart, Lung and Blood Institute, goes to a multidisciplinary team assembled by project principal investigator William Wagner, Ph.D., associate professor of surgery and bioengineering at the University of Pittsburgh School of Medicine and associate professor of chemical and petroleum engineering at the University of Pittsburgh School of Engineering.
"We are working on ways to grow tissues that will not just be similar to our own in terms of their make-up, but also that will be mechanically strong and functional," said Dr. Wagner, who also is a deputy director of the McGowan Institute. "To do this, we will need to train the tissue as it develops for the role that it will ultimately assume."
Such tissue development efforts aim to help the body regenerate its own components needed to repair damage caused by heart attack or underlying disease such as congestive heart failure (CHF), a loss of functional heart muscle. Nearly 5 million Americans are currently living with CHF, according to the American Heart Association. About 550,000 new cases are diagnosed annually. Of those, about 50 percent likely will die within five years.
Significantly, CHF also can substantially diminish quality of life. Because the heart pumps inefficiently, patients can feel breathless and weak after minor exertion. According to the Centers for Disease Control and Prevention, CHF is responsible for about 260,000 deaths a year. In 1995 alone, Medicare paid $3.4 billion for heart failure treatment.
Being able to provide tissue-engineered treatments to increase muscle strength and replace arteries blocked by heart disease could have significant positive impact on patient care.
To reach this goal, planned projects of the grant combine the expertise of University of Pittsburgh faculty in stem cell biology, tissue engineering and imaging in what is called a Bioengineering Research Partnership, added Dr. Wagner. "The great thing about Pitt is that we have these lines of communication already in place through the McGowan Institute."
Both projects establish populations of stem cells from muscles or bone marrow within a polymer that is specially formulated for flexibility and permeability and that biodegrades at a stable rate into non-toxic components in the body. The plan is to use this polymer scaffold as a bridge to generate new, healthy, native tissue.
In one project, a team of surgeons and bioengineers is developing a myocardial patch, which aims to serve as replacement tissue for damaged or diseased heart muscle. The process involves seeding of stem cells onto a biodegradable polymer scaffold and training this tissue for the rhythmic contractions that it ultimately will need to perform.
For the second project, a team led by David Vorp, Ph.D., associate professor in the departments of surgery and bioengineering at the University of Pittsburgh schools of Medicine and Engineering, is working to develop tissue-engineered blood vessels that are a biological and functional equivalent to the patient's own blood vessels, such as those used for coronary artery bypass surgery. Mechanical stresses are being applied to these constructs in order to train them to grow and function similarly to natural blood vessels.
Related projects will track the development of these treatment options on a molecular level, measuring biological markers of stem cells to establish differentiation into appropriate cell lineages, including cardiomyocytes, smooth muscle cells and endothelial cells. These cells are among the main components of heart muscle and blood vessel construction. Cell components will be tagged with fluorescent proteins that can be targeted by imaging technologies to follow the development of the cells and tissues after they have been placed in the body. Project scope will encompass in vitro and preclinical studies of tissue-engineered products.
In addition, discoveries made in the course of this research could benefit tissue-engineering efforts aimed at disorders that involve other "mechanically active tissues," such as the bladder and urethra, said Dr. Wagner, adding that researchers hope to be close to the brink of clinical trials in terms of refining techniques at the close of the five-year grant period.
"This work is a fine example of the unique synergy among research disciplines that define tissue engineering," said Alan J. Russell, Ph.D., director of the McGowan Institute. "At the very least, these projects will significantly enhance our knowledge base about tissue regeneration and controlling tissue structure."