ISIS Press Release 13/01/05
Patient’s Own Stem Cells Mend Heart
Adult stem cells proving themselves in the clinic. Dr. Mae-Wan
Ho reports
A fully referenced version
of this paper is posted on ISIS members’ website.
Details here
From lab to clinic
Over the past three years, adult stem cell research has been moving from
the lab to the clinic with a string of promising outcomes in treating
conditions such as chronic arthritis, severe systemic lupus
erythematosus, Crohn’s disease, cancer, and repairing damaged heart
after heart attack (see "Hushing up adult stem cells",
SiS 13/14;
"Human cloning & the stem cell debate",
SiS 16).
Follow-up research in several laboratories have now confirmed that stem
cells in the bone marrow or circulating in the bloodstream are indeed both safe
and effective in heart repair, helping to recover the heart’s ability to
contract properly to deliver oxygen and nutrients to the rest of the body.
Non-surgical treatment with patient’s own cells
After a heart attack, the muscle cells at the periphery of the damaged
area tend to overgrow in order to make up for the dead or damaged cells. But
this initiates a further loss of muscle cells, causing the damaged area to
expand and to be replaced by useless scar tissue, eventually ending in heart
failure. Many drugs are aimed at preventing this process of ‘cardiac
remodelling’ after a heart attack, so as to stop the heart muscle cells
from overgrowth and dying.
Researchers at Heinrich-Heine-University of Dusseldorf in Germany, who
reported the first success in repairing a patient’s damaged heart three
years ago, have since treated ten more patients, all male, by transplanting the
patients’ own bone marrow cells (BMCs). The BMCs, collected the day
before, purified and expanded in culture overnight, were introduced into the
blocked (infarct) artery that precipitated the heart attack during balloon
dilatation of the artery that’s part of the standard treatment. Another 10
male patients, who refused the cell therapy, were treated with the standard
therapy only.
After 3 months follow-up, the damaged region was found to have decreased
significantly in the group receiving BMC therapy, from 30+13 to
12+7%, and significantly smaller than the standard therapy group.
Similarly, the damaged wall movement velocity increased significantly only in
the cell therapy group, from 2.0+1.1 to 4.0+2.6cm/s. There were
also significant improvements in the cell therapy group that reflected the
heart’s ability to contract properly and deliver blood to the body.
The regeneration of healthy muscle tissue in the damaged area was
accompanied by the formation of new blood vessels. An important contribution to
the success of the treatment, the researchers pointed out, was the use of a
non-surgical procedure thus avoiding risks associated with surgical operations.
The introduction of cells through the infarct artery also ensured that cells
would be transported to areas requiring tissue regeneration.
Stem cells from blood just as effective
In a further study, the same researchers compared the effect of BMCs
with progenitor cells purified directly from the blood. In this protocol, 20
patients were randomly assigned to receive either of the treatments twenty-four
hours after heart attack.
Patients receiving BMCs had their bone marrow aspirated on the morning
of the day of cell transplant, and the cells were used directly after
purification without expansion in culture. Those receiving blood progenitor
cells had 250ml of blood collected immediately after random assignment.
Mononuclear cells were purified and cultured for 3 days before being re-infused
into the infarct artery.
Both treatment groups improved significantly in the measured parameters
of heart function after 4 months; there were no difference between the two
groups in the extent of improvement.
In contrast, the control group (of 11) who did not receive cell therapy
showed no significant improvement in any of the same parameter at 4 months.
A randomised trial
Another research team at Hannover Medical School in Germany carried out
a randomised trial on the BMC therapy. Here, 60 patients were randomly assigned
in equal numbers to either a control group that received optimum post-infarct
medical treatment, or BMC (direct, no expansion in vitro) transplant at
about 5 days after similar coronary intervention. The endpoint measurement was
the change in global left ventricle ejection fraction (LVEF) from baseline to 6
months’ follow-up, as determined by cardiac MRI (magnetic resonance
imaging).
Global LVEF at baseline, determined at about three and a half days after
post-infarct medical treatment was 51.3 +9.3% in controls and 50.0 +10.0% in
the BMC group. After 6 months, however, mean global LVEF had increased only
0.7% in controls compared to 6.7% in the cell group.
The researchers concluded: "The effects of cell transfer were over and
above benefits associated with established strategies to promote functional
recovery after acute myocardial infarction", which included both physical and
pharmacological interventions.
Mechanisms debated
Other researchers have cast doubt on whether the ability of bone marrow
cells to mend damaged heart depends on the stem cells found in the bone marrow
developing into heart muscle cells or capillaries (fine blood vessels) or both;
but that does not detract from the positive results obtained in the trials.
Researchers at Columbia University, New York, recently isolated from
adult human bone marrow, endothelial progenitor cells or angioblasts that
migrate to ischemic (blood-flow deprived) myocardium (muscle wall of the
heart), where they induce new blood vessel formation and prevent myocardial
remodelling.
They have now shown in experiments on rats that increasing the number of
human angioblasts to the infarct area induced a dose-dependent new blood vessel
formation with development of progressively larger-sized capillaries. This
results in sustained improvement in cardiac function by protecting against cell
death, and inducing proliferation and regeneration of the rat heart muscle
cells.
The researchers suggest that in the cardiac remodelling process after
heart attack, those heart muscle cells that overgrow to compensate for the dead
cells eventually die because the capillary network cannot provide the increase
in blood flow necessary for the cells to survive.
Thus, agents (possibly chemical) that increase bone marrow angioblasts
homing in on the heart muscle to form new blood vessels could effectively
induce endogenous heart-muscle cells to enter the cell cycle and help the heart
regenerate and recover.
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