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Healing the Heart with Bone-Marrow Cells

A new treatment may help angina sufferers who are resistant to surgery and medication.

Injecting the hearts of angina sufferers with cells extracted from their own bone marrow can reverse the condition and relieve its symptoms, a new study suggests.

Free flow: These images show a patient’s left ventricle before treatment (on the left) and after (on the right). The top images were captured after exercise and the bottom ones show the ventricle at rest. Increased blood flow is indicated by more orange.

The Dutch cardiologists behind the placebo-controlled study say that the results may lead to radical new treatments for patients for whom surgery and medication bring little or no relief from this painful and debilitating condition, which results from narrowed arteries that cannot supply enough blood to the heart during exercise. All 50 subjects involved in the study were resistant to existing treatments.

Three months after being given the injections, patients’ hearts were less starved of blood, and they were able to exercise more, researchers report in the latest issue of the Journal of the American Medical Association.

Lead researcher Douwe Atsma, a cardiologist at Leiden University Medical Center, in the Netherlands, hopes that follow-up studies, which are currently in progress, will also reveal lower death rates among those who received the treatment.

Atsma’s team first fed catheters through patients’ femoral veins, up into the aorta, and then into the heart’s left ventricle–the chamber that pumps oxygen-rich blood back in the circulation. By touching an electro-sensitive tip around the chamber’s surface, the researchers were able to locate areas of low electrical activity, where diminished blood supply had caused cells to die. They built up a “map” of the left ventricular surface of all 50 patients.

The researchers then took bone marrow from participants’ hips and extracted the mass of mononuclear cells–an ill-defined mix of stem cells and progenitor cells.

In 25 of the patients, the researchers injected around 100,000 cells into angina-affected areas on the ventricular surface, using a modified form of the same catheter. The remaining 25 patients received a placebo injection of saline.

Three months after the treatment, more catheter tests showed that the average number of diseased grid areas in the hearts of treated patients had fallen from 4.2 to 1.8, or 57 percent. In patients given the placebo, the number fell from 3.8 to 3.1–a significantly smaller 18 percent reduction.

Bone-marrow recipients were also able to expend more energy on an exercise bike after three months: 114 kilocalories, compared with 107–a small but significant change. Placebo patients experienced an improvement of just 101 kilocalories compared with 99.

Earlier trials in which researchers sought to treat heart-attack victims with their own bone-marrow cells produced mixed results. Some studies found moderate improvements in a few measures of heart function, but none showed a clear health benefit.

Atsma notes, however, that angina is very different from a heart attack. “People who’ve just had a heart attack need instant methods to remove blockages, as tissue starts to die and all sorts of inflammatory processes are being unleashed,” he says. “It may be that cell injections are best suited to the treatment of chronic heart conditions such as angina. In using this method to treat angina, you are treating the underlying cause of a chronic condition over weeks and months.”

Atsma hopes that follow-up research will demonstrate that angina patients who receive the treatment are less at risk from associated conditions, particularly abnormal heartbeats, or arrhythmias, which kill thousands every year. He says that the small but significant improvement in blood supply seen in the placebo group suggests that the act of pricking the heart lining may encourage growth of new blood vessels.

The researchers are now investigating which types of bone-marrow cell best help repair the heart. One theory is that a type of progenitor cell called a mesenchymal cell, which gives rise to muscle and bone tissue, might encourage the growth of new blood vessels by releasing growth factors. “But the truth is we don’t really know which cells–or which combination of cells–are having the effect,” Atsma says.

Stefan Janssens, a cardiologist and research scientist at University Hospital Gasthuisberg, in the Netherlands, is also investigating bone-marrow treatment for heart disease, and he says that the study succeeded in demonstrating that cell injections increase blood supply to the heart. “This is a good study, and it’s important that it’s randomized and double-blinded,” he says.

But Janssens also notes that it sheds little light on the exact mechanism of the treatment. “The injected cells are probably encouraging the growth of new blood vessels indirectly by producing growth factors. But it’s not possible to rule out that they are improving the condition of old vessels.”

Janssens says that boosting blood supply alone would not help the huge number of patients with heart failure, a deadlier condition in which injured hearts swell and pump blood less effectively. “For these patients, we need to know which cells will allow them to grow new heart muscle,” he says.

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