Research killed by lethal injection

Clinical trial on stem cells in coronary patients had to be halted due to incidents of restenosis

By Graham Furness

Research into stem cells, often proposed as a panacea for a range of diseases, may have hit a bump in the road over the issue of uncontrolled growth of new tissue, after research published in the March 6 issue of The Lancet was stopped early because of a potentially lethal adverse effect.

Stem cells have been proven to improve cardiac function in patients who've suffered heart attacks by stimulating the growth of new blood vessels in the myocardium. But harvesting stem cells from bone marrow is a highly invasive procedure.

A new technique involves injecting the patient with granulocyte-colony stimulating factor (G-CSF), a glycoprotein which stimulates the bone marrow to pump blood stem cells into the circulation. A group of Korean researchers recently used this method to introduce stem cells to heart attack patients who had previously been treated with coronary stents.

While the stem cells did their job in forming new blood vessel tissue, they displayed an unfortunate tendency to generate new tissue at the site of the stent itself, risking closure of a major coronary artery.

In the latest study, Dr Hyo-Soo Kim and his colleagues at Seoul National University injected 20 patients who'd suffered heart attacks with G-CSF. Ten of them had stem cells filtered and purified from their blood, and then introduced into their heart. The remaining 10 were observed to see what effect the extra stem cells generated by G-CSF in their circulation might have without outside intervention. A further seven patients were observed as controls.

After six months, those injected with the purified stem cells were able to run further on a treadmill than the control group. They also showed significantly better systolic function and myocardial perfusion. The group treated with G-CSF alone showed no such improvements.

Unfortunately, in seven of the 20 patients injected with G-CSF, angiogenesis took the form of potentially dangerous restenosis. The stem cells stimulated by G-CSF may have accumulated at the stents and transformed into new tissue, the Korean team suggested.

Dr John Martin of University College London, who is also spearheading stem cell trials, said the results were "concerning." But he added that the small number of patients in this study preclude a final judgement. Problems might be avoided, he said, by tweaking protocols.

Animal experiments have yet to show exactly how stem cells repair the heart. They may generate new heart muscle, encourage new blood vessels to grow or secrete molecules that boost tissue survival. "We don't really know what we're doing," said Dr Martin. But while coronary heart disease remains the world's leading killer, there will always be reasons to push on regardless.