How adult stem cells injected into heart improve its function
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Growth of new blood vessels was seen 3-6 months after stem cells were injected into the heart
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Photo: M. Vedhan
OPERATION REVIVAL: Regeneration of weakened heart muscles using stem cells is possible says Dr. Amit N. Patel, Director of the Center for Cardiac Cell Therapy, University of Pittsburgh Medical Center.
HE IS the only person so far to get the U.S. Food and Drug Administration's (FDA) approval to undertake clinical trials for treating heart patients by directly injecting adult stem cells into the heart. The stem cells are derived from the bone marrow.
And the person who enjoys this distinction is Dr. Amit N. Patel, Director of the Center for Cardiac Cell Therapy, University of Pittsburgh Medical Center.
Others who have got an FDA approval to treat heart patients using adult stem cells supply the cells through an artery using a catheter.
Dr. Patel was in Chennai recently on the invitation of the Chennai based Asia Cryo-Cell that is into cord blood banking.
With the U.S. Government's aversion to embryonic stem cell research due to religious sentiments, all FDA approvals, including Dr. Patel's, have been for using adult stem cells for treating heart patients.
Stem cells are primitive cells capable of becoming any of the specialised cells found in body tissues. Compared with adult stem cells, embryonic stem cells are regarded to be better equipped to become any of the specialised body tissues.
Trial with a difference
Dr. Patel has two ongoing clinical trials. And his first clinical trial that started in 2004 is a clear departure from the conventional trials undertaken so far.
While it is known that hearts treated with autologous adult stem cells show improved functioning to varying degrees, the exact mechanism by which this is brought about is largely not known. This has been one of the biggest lacunae in stem cell research.
Unlike animal studies where the heart is removed for examination during the trial, understanding the ways by which patient's own adult stem cells, which are either injected or provided through arteries, improve the heart's functioning in humans has not been possible.
Dr. Patel and his team have taken a road less travelled to address this lacuna.
He had injected adult stem cells into the hearts of five volunteers who would eventually undergo heart transplantation after a few months.
Removing and studying the hearts that have been injected with adult stem cells a few months prior to transplantation is coming as close as to harvesting hearts from animals that are under trial.
"This will give an opportunity to evaluate the mechanism of the cells [in improving the heart's pumping capability] delivered into the human heart," he noted. "This is the primary endpoint of the study."
To make it a kind of placebo-controlled study, only one part of the heart got stem cells while the other did not. However, there is currently no way of preventing injected stem cells from travelling to surrounding areas.
"There is a large space where cell injection and control injection take place," he explained. "That is currently the only method [available] until we advance to a randomised trial."
Dr. Patel already has some of the answers from the four hearts that have been removed since the trial had started.
Angiogenesis seen
"We are seeing growth of new blood vessels — angiogenesis," he explained. "The angiogenesis is significant." The hearts were removed 3-6 months after the stem cells were injected. It remains to be seen if improved ejection factor comes from angiogenesis even when the stem cells are injected into the arteries.
But in the first place, how does Dr. Patel know where to inject the stem cells. Quite simple — the weakened muscles of the heart.
Weakened muscles
According to Dr. Patel, coronary heart disease usually progresses over many years and this results in general weakening of the heart muscles.
Also, many patients suffer from many minor attacks before the major one strikes. And every minor attack weakens the heart muscles. Weakened heart muscles tend to reduce the ejection factor — ability of the heart to pump oxygenated blood to the rest of the body.
Injecting stem cells where full thickness scars are found is of little use as the scars have no blood supply and hence no nutrition. "Regeneration is possible where muscles are weakened," he said, explaining the rationale for injecting stem cells in the weakened muscles.
Second trial
The objective of the second clinical trial that was started a year ago goes one step ahead — inject stem cells into the heart muscles while the patient undergoes bypass surgery.
"The stem cells are injected into the small diseased [blood] vessels where bypass can't be done," Dr. Patel explained.
The overall aim is to ensure that the heart's blood pumping capacity increases. One of the main objectives is to see which dosage of stem cells will produce the best results.
To that effect, the volunteers will be randomly assigned to one of the four groups, of which one will receive just a placebo. So far ten volunteers have been recruited; the target is 24.
Stem cell therapy
He is optimistic that routine stem cell therapies for certain types of heart disease will become a reality in 3-5 years' time.
Though immediate improvement of the ejection factor following stem cell injection can be used as a criterion to assess the success of the procedure, he does stress that the volunteers need to be followed up for five to ten years to really study the long-term effects.
R. PRASAD
in Chennai
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