Adult Stem Cell Research at UB Targets Damaged Hearts

BUFFALO, N.Y. -- A specialist in stem cell biology at the University at Buffalo has received a $1.98 million grant from National Institutes of Health to investigate the potential of bone marrow-derived adult stem cells to treat the serious heart malfunction known as hibernating myocardium.

Hibernating myocardium is a condition in which heart cells that have experienced reduced blood flow over an extended period of time due to narrowed coronary arteries adapt to this deprivation by down-regulating metabolism while remaining functionally viable.

Previous work in UB's Center for Cardiovascular Research employing the center's novel swine model of hibernating myocardium has shown that restoring normal blood flow to these "hibernating" regions improves function. However, these results also found that cells in the left ventricle, the heart's main pumping chamber, often do not return to normal, leaving the heart compromised.

The new research is headed by Te-Chung Lee, Ph.D., associate professor of biochemistry in the School of Medicine and Biomedical Sciences and an investigator with the cardiovascular research center.

Lee and colleagues will use the swine model to investigate whether transplanting the model's own bone marrow mesenchymal stem cells (MSC) -- cells that have the capacity to develop into blood vessels, as well as other types of tissues -- into the down-regulated tissue can change the myocardial adaptive responses and improve the function of the hibernating myocardium.

"My colleagues and I already have carried out initial stem-cell transplantation studies with promising results," said Lee. "Additional studies will be needed to determine whether and how stem cell populations isolated from aged animals may be used.

"In the long-term, the translation between the MSC-based therapy in the porcine hibernating myocardium and regenerative medicine for humans with chronic coronary artery disease will lead to optimized MSC therapeutics that can be of clinical value in managing aging and curing disease," he said.

The research will be carried out in two phases. During the first phase, investigators will conduct extensive studies of the characteristics and potential of the targeted stem cells, including research on the influence of aging on the potency of MSCs (hibernating myocardium typically does not occur in young persons).

"If aging indeed impairs the function of these adult stem cells," said Lee, "genetic and tissue engineering might be used to boost the competency of aged MSCs."

He noted also that mesenchymal stem cells do not appear to generate a strong immune response. "If this characteristic is proven rigorously," he said, "and if we determine how these stem cells differentiate into cells for specific 'jobs,' it might provide the basis for 'off-the-shelf' use of these stem cells in future therapeutic applications."

The second phase of the project will involve injecting the stem cells into swine with hibernating myocardium. The researchers will track the cells' progress, evaluate their feasibility, and determine if cells engineering for enhanced survival, blood vessel regeneration and "homing potential" (the tendency to migrate properly to the heart rather than elsewhere) can better improve blood flow and tissue function in hibernating myocardium.

Other investigators involved in this multidisciplinary research project are John M. Canty, M.D., Albert & Elizabeth Rekate Professor of Medicine, director of the Center for Cardiovascular Research and a researcher with UB's New York State Center of Excellence in Bioinformatics and Life Sciences, and Gen Suzuki, M.D., Ph.D., research scientist in the Department of Medicine and the cardiovascular center.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. The university is in full compliance with mandates of state and federal regulatory agencies pertaining to the humane use and care of research animals.