UM myoblast transplant team
University of Maryland physicians are taking part in a groundbreaking, multi-center study that could open a new range of treatment options for congestive heart failure. They are investigating whether cells from a patient’s leg or arm muscle, when injected into that person’s ailing heart, can function as new muscle cells to improve the heart’s ability to contract and pump blood throughout the body.
Damaged or scarred cardiac muscle cannot repair itself, but basic research has shown that a type of stem cell called a myoblast, found in the skeletal muscles of the arms and legs, can assume some of the functions of cardiac cells.
“The concept is almost like science fiction,” says Vasken Dilsizian, M.D., professor of medicine and radiology at the University of Maryland School of Medicine and director of Cardiovascular Nuclear Medicine at the University of Maryland Medical Center. “The purpose of our study is to see whether these cells, after they have been harvested from the skeletal muscle and transplanted in the heart, can mature and survive.”
“Small blood vessels adjacent to the scarred areas should supply fuel and nutrients for the cells, and with time they may multiply, contract and cause the heart muscle to work normally again,” adds Dr. Dilsizian, who is principal investigator of the study at the University of Maryland.
“This concept is similar to the salamander tail that re-grows after it is detached,” says co-investigator Bartley P. Griffith, M.D., chief of Cardiac Surgery at the University of Maryland Medical Center and professor of surgery and head of the Division of Cardiac Surgery at the University of Maryland School of Medicine. “We believe this is the beginning of learning how the heart may heal itself.”
The challenge for cardiologists and cardiac surgeons is to restore function to heart muscle damaged by a heart attack. In a heart attack, a blood vessel is blocked, disrupting the flow of blood to the heart muscle, which causes it to die. Over time, this can lead to heart failure, which is the inability of the heart to pump enough oxygen- and nutrient-rich blood to meet the body’s needs. About five million Americans are living with heart failure. Approximately 550,000 new cases are diagnosed each year.
“We can’t prevent all heart attacks from occurring, but we may be able to reduce the harmful effects of a heart attack, by replacing damaged tissue with cells that grow into muscle,” says Dr. Griffith.
For this study, a Phase 1 clinical trial to evaluate the safety of the treatment, the myoblast transplantation is done in combination with coronary artery bypass grafting (CABG) in patients who have had a heart attack, and whose ejection fraction, a measure of the heart’s pumping ability, is less than 40 percent.
The myoblasts begin their journey to the heart when a thimble-sized sample of muscle from the patient’s thigh is taken about six weeks before the CABG surgery. The sample is sent to a processing facility where the cells are isolated and grown in culture to produce 300 million cells. The cells are returned to the hospital where they are infused by injection in and around the damaged heart muscle on the day of surgery.
Because the myoblasts come from the patient and go back to the same patient, this procedure, called an autologous transplant, avoids the risk of graft rejection.
Doctors employ advanced magnetic resonance imaging (MRI) to pinpoint where the cells will be implanted. Dr. Griffith says that when he transplanted the cells for the first patient in the study at the medical center, he infused the cells through 18 injections.
Dr. Dilsizian will use a variety of advanced imaging techniques to track the progress of the transplanted myoblasts during a two-year follow-up. Patients will be given monthly and sometimes weekly imaging and blood tests. State-of-the-art imaging, including positron emission tomography, MRI, and echocardiography will be used to look for changes in blood flow, metabolism and function.
The study may also help to refine how cardiac cell growth is detected. “Besides examining the progress of the cells, we will also be raising questions of imaging, such as what is the best way to show the cell growth, what are the best techniques?” says Dr. Dilsizian.
Dr. Griffith says this study represents the early stages of understanding how this treatment may work. “We have to determine which are the best cells to use, and how to encourage them to grow,” he says. “Ultimately, we hope to restore the heart’s pumping function by integrating the new cells both electrically and physically with the heart’s own tissue and muscle cells.”
The study, conducted at five medical centers around the U.S., is funded by GenVec, Inc., a biopharmaceutical company.
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