Research Highlights
Adult-stem-cell therapy to be tested as adjunct to heart surgery
September 5, 2007
Researchers at the Salt Lake City VA and the University of
Utah are gearing up to test whether patients undergoing
bypass surgery for coronary artery disease will gain added benefit
from an injection into the heart of adult stem cells, harvested from
their own hip bone just prior to surgery. The trial will involve 18
veterans.
According to cardiac surgeon and lead investigator G. Russell
Reiss, MD, the addition of stem cells should help boost heart function
and improve quality of life. His team will use echocardiography,
cardiac MRI and other tests to track outcome measures such
as ejection fraction (EF), an indicator of how well the heart pumps
blood. He expects bypass patients who receive the stem cell injection
to see an increase in their EF of more than six percent, compared
with bypass patients who receive only a placebo injection.
"Probably the most profound effect or benefit that patients
could experience from an increase in EF is in their overall quality
of life," says Reiss. "People below 40 percent begin to realize
real limitations in exercise and their ability to perform activities of
daily living. Those with EFs in the 20s can be severely restricted
or disabled. Fortunately, stem cells have been shown to help those
with the lowest EFs the most. That is why we are focusing on
patients with EFs less than 40 percent."
Stem cells like 'little fire rescue boats'
Scientists have learned that contrary to popular notion, the main
way in which stem cells regenerate tissue is not by morphing into
the type of cell that was lost or damaged—in this case, myocytes,
or muscle cells. Rather, they promote the healing of other cells.
"They probably function best by helping save existing myocytes
from death, not by creating new ones," explains Reiss. "They seem
to work like little fire rescue boats loaded with cytokines, growth
factors and anti-apoptotic factors that they can deliver to highly
specific areas of injury and inflammation, helping to stabilize the
whole area at a cell-to-cell level."
Reiss said the stem cells also seem to "stabilize the cytoskeleton
of the heart and act as a 'functional patch' to maintain the proper
geometry of the heart, which is very critical to the overall performance
of the heart as it undergoes remodeling from injury."
The phase 1 trial, funded by VA, will get under way even as
Reiss and colleagues continue to perform animal experiments to
further expand and refine knowledge of how the stem cells work.
"Regenerative medicine, which includes stem cell therapies, is a
highly translational field and there is a great deal of bench to bed-side and back to the bench that takes place," he said. "Most investigators
involved in these trials will need expertise both in the animal
lab and with conducting human clinical trials." He emphasized that
human trials are conducted only after the therapy has been shown
to be safe in animals.
The clinical trial will involve a graded approach in which higher
doses of stem cells—up to 100 million cells—will be administered
to patients enrolled in later stages of the study, after lower doses
have proved thoroughly safe.