Hearts damaged by lack of blood supply can be mended by the body's own bone marrow cells, researchers have now demonstrated. This gives the lie to the claim that embryonic stem cell research is necessary. Dr. Mae-Wan Ho reports.
Sudden blockages of a major artery to the heart cuts off blood supply and lead to rapid death of the muscle cells and blood vessels in the heart. This condition, myocardial infarction, is a common form of heart disease. Despite the demonstration that some of the heart muscle cells can multiply and new vessels formed, regeneration is restricted to the living part of the heart wall. The 'infarcted' or dead area is irreversible, and in time, scar tissue is formed. Attempts to replace the dead tissue by transplanting heart muscle cells or skeletal muscle cells have failed to mend the damaged part properly.
In previous experiments on mice, researchers in New York Medical College and the National Institute of Health injected bone marrow cells along the border of the damaged area of the heart, and found that the cells did differentiate into muscle and blood vessels. But this surgical intervention killed a high number of the mice and the grafting success was only 40%. This prompted them to consider a 'non-invasive' method, which involved stimulating the mice to overproduce bone marrow cells before and after myocardial infarction was induced .
For the purpose, the mice were given daily injections of two cytokines (small molecules that influence the activities of cells), stem cell factor (SCF) and granulocyte-colony-stimulating factor (G-CSF), which increased the number of circulating stem cells two to three hundred fold.
Mice given cytokines had a survival rate of 73% after the operation, compared with 20% in controls not given cytokines. There were clear signs of repair in the damaged area of the heart in the cytokine-injected group, both new heart muscle and blood vessels were formed, whereas only scar-tissue was found in controls. The hearts of the cytokine-injected group also performed significantly better than the controls.
The experimental results looked impressive enough even though the protocol of inducing myocardial infarction in such large numbers of animals is debatable. In addition, there was an unaccountably small number of experimental animals, only 15 compared to 52 in the group of controls. This may be because the researchers excluded mice that died within 48h of the operation, "to minimize the influence of the surgical trauma". But could it be that the mice died from stress of overproduction of bone marrow cells caused by the cytokines injected? There are certainly more ways to be invasive; and much more effort should be devoted to reducing unnecessary and stressful interventions, both physical and chemical.
It is most important to clarify the effects of the cytokines before these are recommended for clinical trials.
Article first published 24/08/01
1. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A and Anversa P. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. PNAS Early Edition http://www.pnas.org/cgi/doi/10.1073/pnas.181177898
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