Cell transplantation has the potential to become but one of the new and exciting therapies for the treatment of patients with chronic heart failure.
Although we have seen tremendous advancements in the treatment of all types of cardiovascular disease that may progress to heart failure, we continue to see a rapidly growing incidence of heart failure. What accounts for this expanding problem?
One explanation may be that although many kinds of heart disease can be successfully treated, they are not truly cured. A good example is the patient who has an acute myocardial infarction (heart attack, MI) with significant myocardial (heart muscle injury). While reperfusion therapy, such as angioplasty or coronary artery bypass grafting, will prolong survival, the permanent myocardial damage may lead to changes in the heart's left ventricle, resulting in heart failure.
The body has an amazing ability to repair itself. When injury occurs, the body sends special cells (natural stem cells, produced by the bone marrow) to the site that calls for healing. These cells, help remove dead cells and repair the injured tissue. For some reason, the heart does not have the same process for healing itself.
In the past decade, researchers have been testing the ability to utilize cells to rebuild the heart after injury. Early research looked at transplantation of fetal or embryonic stem cells, as well as myoblasts (immature muscle cells). While fetal stem cells have promise, the widespread clinical application of this approach is limited due to the ethical dilemma of the use of embryonic and fetal tissue as well as the issue of chronic rejection.
The skeletal muscle cells, an autogenic source, recovered from the recipient's own body, have the advantage of being a readily available and unlimited source without the risk of rejection. The myoblasts are harvested from the patient's thigh, processed in the lab, and injected into the heart. Prior studies showed that processed myoblasts demonstrate the ability to become functioning heart muscle cells, as well as proliferate and send signals to attract additional stem cells to repair damaged heart muscle.
A small pilot study was conducted last year at the Cleveland Clinic, using cells obtained from the patient's own leg or arm muscles to create millions of skeletal muscle cells, and implanted into the diseased heart muscle during bypass surgery, in patients with heart failure. This was the first step down the road to determine if cell therapy can be used to repair damaged hearts.
The Cleveland Clinic continues to investigate the use of cell therapy. Another small pilot study is investigating the use of skeletal muscle cells injected in participants with heart failure, who are having an internal defibrillator implanted. A study, using catheters to inject skeletal muscle cells during interventional procedures, will be coordinated by Drs. Stephen Ellis and Patrick Whitlow in Fall of 2004.
Marc Penn MD, Ph.D., has been leading research at the Cleveland Clinic to determine why the heart does not initiate the same signaling process for healing as other tissues in the body. In research published in the Lancet last year, Dr. Penn identified "stromal cell derived factor 1," or SDF-1, a biochemical signal that calls for stem cells to go to the heart. The effect of SDF-1 is short, however, only lasting a few days after a heart attack - not enough time to heal itself. Future research will look at how to utilize the model of SDF-1 to increase the amount of stem cells traveling to the heart. Researchers harvest myoblasts from lab animal's thigh, then genetically modify the cells to send out biochemical signals. When the modified cells are re-injected into the heart, the internal stem cells pick up the signal and travel to the heart muscle. Early lab studies have shown an increase in heart function. Dr. Marc Penn is planning a trial of Cleveland Clinic developed stem cell therapy for patients, mid to late 2005.
Glossary of terms:
Allogenic: from one person to another (for example: organ transplant)
Autogenic: use of one's own tissue
Myoblasts: immature muscle cells, may be able to change into functioning heart muscle cells.
Stem Cells: cells that have the ability to reproduce, generate new cells, and send signals to promote healing.
Transgenic: Use of tissue from another species. (for example: some heart valves from porcine or bovine tissue)
Resources:
- Arman T Askari, Samuel Unzek, Zoran B Popovic, Corey K Goldman, Farhad Forudi, Matthew Kiedrowski, Aleksandr Rovner, Stephen G Ellis, James D Thomas, Paul E DiCorleto, Eric J Topol, Marc S Penn. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. The Lancet *, Volume 362 Issue 9385 Page 697.
- Hopes Rise for Cell Regeneration, Heart Advisor, Volume 7, Number 7, July 2004, p. 4-5. For subscriber and customer service information, write to Heart Advisor, P. O. Box 420235, Palm Coast, FL 32142-0235 or call toll free at 800/829-2506.
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