The LateTIME study (Transplantation In Myocardial Infarction Evaluation) rigorously examined the safety and effectiveness of whole bone marrow cell transplantations into the heart after a heart attack. This study definitively established the safety of this procedure, but it was not able to demonstrate the effectiveness of it.
LateTIME study participants received bone marrow transplants two-three weeks after suffering from a heart attack. Between July 2008 and February 2011, 87 people who had suffered heart attacks were enrolled in the LateTIME study. All patients had undergone cardiac procedures to open blocked arteries, and had moderate to severe impairment in their left ventricles, the heart chamber that pumps oxygen-rich blood from the heart to the systemic circulation where the blood flows through the body. All participants had stem cells taken from bone marrow in their hip for processing. LateTIME researchers developed a standardized method of processing and purifying bone marrow stem cells, and this was the first BMC trial to provide a uniform dose of BMCs to each participant. The study also randomly assigned the participants to receive either their purified BMCs or inactive (placebo) cells.
Several previous studies have suggested that injecting BMCs into the heart can improve cardiac function following a heart attack and perhaps reduce the need for future hospitalizations and heart surgeries. In contrast to LateTIME, earlier studies delivered BMCs within a few days of the heart attack. In many cases, a patient will not be able to get such immediate treatment, due to poor health following a heart attack or because the hospital providing care doesn’t have a stem cell therapy program.
“Although treatment and survival following a heart attack have improved over the years, the risk of heart failure following a heart attack has not decreased,” said Susan B. Shurin, M.D., acting director of the NHLBI. “Stem cell therapy is a promising direction for repairing the damage done by a heart attack. We do not fully understand the optimal use of these cells; studies like LateTIME will help us understand how to perform and monitor these procedures.”
After six months, improvement of heart function was assessed by measuring the percentage of blood that gets pumped out of the left ventricle during each contraction (left-ventricular ejection fraction, or LVEF) by cardiac MRI. There were no significant differences between the change in LVEF readings between baseline and six months in the BMC (from 48.7 percent to 49.2 percent) or placebo (from 45.3 percent to 48.8 percent) groups.
“This does not mean that stem cell therapy will only work if done immediately following a heart attack or that later beneficial effects on clinical outcomes won’t emerge,” noted Lemuel A. Moyé , M.D., Ph.D., professor of biostatistics at the University of Texas School of Public Health, Houston, and a LateTIME researcher. “Many factors influence how the heart responds to stem cells, which highlights the critical need to continue rigorous tracking studies in this area.” Moyé also added that the health of the study participants will continue to be evaluated for two years, so the BMC therapy may yet demonstrate health benefits such as a lower risk of subsequent heart attacks or heart failure, in which the heart cannot pump enough blood to meet the body’s needs.
LateTIME is one of three heart stem cell trials being undertaken by the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network. The other trials under way by this multicenter consortium are TIME, which compares the effectiveness of stem cell therapy delivered at three days versus seven days following a heart attack, and FOCUS, which examines stem cell therapy in people with chronic heart failure.
This study and several others seem to establish that whole bone marrow is simply not as effective for treating heart attack patients as specific stem cell populations. Bone marrow stem cells are a very heterogeneous population, and specific populations of bone marrow stem cells must be isolated, expanded, and conditioned for heart muscle/blood vessel differentiation before they can be used. These specific stem cell populations are almost certainly much more effective than whole bone marrow, which contains a variety of cells that almost certainly cannot survive in the oxygen-poor environment of the heart after a heart attack.