Growth Factor

A drug that stimulates bone marrow to produce stem cells helped regenerate damaged heart muscle in one of the first studies of its kind, according to a report presented at the American Heart Association’s Scientific Sessions 2003.
   The drug, granulocyte colony stimulating factor (G-CSF), treats some forms of cancer. It stimulates bone marrow to produce the different types of blood cells, including white blood cells that can become depleted after disease or chemotherapy.
   G-CSF might help repopulate the heart’s muscle cells, which in turn could help repair the damaged heart, said lead author Chris A. Glover, M.D.
   “Research has shown that there are cells in the heart that come from bone marrow stem cells. We hypothesized increasing these cells after a heart attack may help the heart regenerate heart muscle cells, and this is supported by our results,” said Glover, assistant professor of medicine at the University of Ottawa and the Ottawa Heart Institute in Ontario.
   “The main limitation of this study is that it included only five patients and was not randomized. On the other hand, the study’s strengths are that it explores the use of a novel therapy, which is a simple treatment that any physician could use to improve the outlook for heart attack patients.”
   All five patients who received G-CSF had anterior wall heart attacks, also known as large heart attacks. They had emergency angioplasty, a procedure to open their vessels by inserting an inflatable balloon that compresses the plaque and restores blood flow.
   “We wanted patients with large heart attacks in this study, since they have the most to benefit from a therapy that could regenerate the heart,” Glover said.
   Within two weeks of the patients’ heart attack, doctors injected G-CSF in the fatty skin layers once a day for four consecutive days.
   Researchers measured CD34 cells, a marker of stem cells, to find out if the drug was stimulating stem cell growth. An increase in white blood cells indirectly indicates that G-CSF is working. After four days, blood cells increased about five-fold and CD34 cells increased about 10-fold.
   Before treatment and six weeks after treatment, researchers also measured left ventricular (LV) ejection fraction, which indicates how much blood the heart pumps out of its main chamber. They assessed blood flow and metabolism by positron emission tomography (PET) scan, which measures the heart’s contraction and indicates how much heart tissue is viable.
   All five patients were free of side effects or heart-related complications at six weeks’ follow-up. Also at six weeks, ejection fraction went from 27 percent to 35 percent, and the patients had a considerable metabolic (viable tissue) recovery from 59 percent to 75 percent.
   Co-authors are R.S. Beanlands, R.A. deKemp, K. Mostert, L. Garrard and H. Atkins.