Muscle cell transplants
repair damaged heart tissue
Monday, 18 November 2002
Researchers safely transplanted 16
patients' skeletal muscle cells into their own severely damaged hearts in
the first human testing in the United States, according to a study
reported today at the American Heart Association's Scientific Sessions
"We have been able to regenerate dead heart muscle, or scar tissue, in the
area of heart attack without increasing risk of death," says lead author
Nabil Dib, M.D., director of cardiovascular research at the Arizona Heart
Institute in Phoenix. "Our findings will allow us to move forward with
testing if the procedure can improve the contractility of the heart."
The interim results indicate the procedure is safe and feasible, he says.
When patients suffer a heart attack, scar tissue develops, resulting in a
decrease in heart contractility - its ability to compress and force blood
through its chambers. Since heart cells can't repair themselves, this
damage is irreversible and eventually results in heart failure.
Researchers conducted the multi-centre trial, overseen by the U.S. Food
and Drug Administration, in patients who had suffered heart attacks or
heart failure and whose hearts had reduced pumping ability evidenced by
left-ventricular ejection fraction (EF) less than 30 percent. EF measures
the quantity of blood pumped from the heart with each beat. A healthy
heart pumps out a little more than half the heart's volume of blood with
each beat for an EF of 55 percent or higher.
Eleven patients were undergoing coronary artery bypass surgery (CABG) and
five were having a left ventricular assist device (LVAD) implanted. An
LVAD helps a failing heart until a donor heart becomes available for
The patients' myoblasts cells (immature cells that become muscle cells)
were extracted from thigh muscle. Large quantities of the cells were grown
in the laboratory for three to four weeks using a controlled cell
expansion manufacturing process. During the surgery, one to 30 direct
injections - containing 10 million cells each - were made into the damaged
area of the hearts. The dosages ranged from 10 million to 300 million
"We found that the transplanted myoblasts survived and thrived in
patients. Areas damaged by heart attack and cardiovascular disease showed
evidence of repair and viability," Dib says.
No significant adverse reactions were found related to the cell transplant
procedure in either group of patients in follow-up testing nine months
There was one death due to infection of the device in the LVAD group three
months after cell transplantation, and one patient in the CABG group had
non-sustained ventricular tachycardia - a fast heart rate that starts in
the lower chambers (ventricles).
While the trial was not designed to evaluate the effect of cell transplant
on cardiac function, Dib calls the results extremely encouraging.
Examining the heart by echocardiogram, magnetic resonance imaging (MRI),
and positron emission tomography (PET scan) showed evidence of scar tissue
regeneration in the area of the graft, which indicates repair.
EF rates improved, on average, from 22.7 percent to 35.8 percent - a 58
percent increase - after 12 weeks.
"The important finding in the LVAD clinical study, is that we were able to
directly examine and observe histological changes in the heart muscle of
patients after they received a new heart and their old one was removed,"
The results were also compared against a group of historical controls from
a Yale University study, published in the Journal of the American College
of Cardiology (93:22:1411-7) of 83 patients with EF less than 30 percent
before bypass surgery. In the Yale group, there was a 13 percent overall
death rate and an 11 percent heart death rate at one year.
After bypass, the Yale group's EF improved from 24.6 percent to 33.2
percent - a 36 percent increase.
At Scientific Sessions 2000, French researchers described the first human
experience with autologous skeletal myoblast transplantation. The
transplant improved EF in a 72-year-old man undergoing a bypass procedure.
Subsequent procedures in other patients have been reported at other
meetings. Those studies showed similar improvement in viability of dead or
damaged heart tissue, but several adverse reactions, such as
life-threatening arrhythmias also were reported.
No such complications were found in this study, Dib notes.
Other promising cellular and molecular procedures are being explored as
ways to repair and strengthen the damaged heart by replacing dysfunctional
or dead heart cells with cells from other sites and those grown in
laboratories, Dib says. These include embryonic and adult cardiomyocytes,
embryonic stem cells, genetically altered fibroblasts, smooth muscle
cells, bone marrow-derived cells, and adult skeletal myoblasts.
American Heart Association Press Release