Autologous bone marrow–derived intracardiac stem cell therapy after revascularized acute MI "seems to be safe and improves heart function moderately but significantly," according to a review and meta-analysis of all randomized controlled trials of the treatment done through 2011, which was published online Feb. 14 by the Cochrane Collaboration.
This form of intracardiac stem cell therapy improves global left ventricular function and reduces infarct (scar) size – changes that persist in the long term. Nevertheless, because morbidity and mortality are so low in this patient population, there is no evidence yet that this experimental treatment has any significant effect on these outcomes, said Dr. David M. Clifford of the stem cell research lab at the University of Oxford (England), and his associates.
It is hoped that ongoing research will provide the data to answer the crucial question of whether bone-marrow stem-cell therapy actually improves morbidity, mortality, and quality of life, they noted.
Investigators for the Cochrane Collaboration previously published a review of this topic in 2008, and research since then has progressed to the extent that an updated Cochrane Review of safety and efficacy was called for. The previous review evaluated 13 studies, almost all of which had only short-term follow-up. A total of 20 more studies are now available, with follow-ups as long as 5 years.
Dr. Clifford and his colleagues reviewed the literature and performed a meta-analysis of these 33 randomized clinical trials involving 1,765 subjects. These studies were conducted in 17 countries in 2004-2011, and 13 of them are still ongoing.
All the study subjects underwent either PCI, thrombolysis, or both as the primary treatment for MI. Most of the trials compared adjuvant stem cell therapy against no further intervention, but some compared it against an active intervention with placebo infusions.
Pooled results demonstrated that this form of stem-cell therapy significantly improves left ventricular function, reducing left ventricular end-systolic and end-diastolic volumes as well as infarct size and cardiac wall motion. These benefits persisted throughout long-term follow-up.
Moreover, the improvements correlated with the amount of stem cells infused, so that an increasing dose yielded increasing benefit.
"The results of all trials together suggest a small reduction in the incidence of mortality and morbidity, in favor of [stem-cell therapy], but this finding is not statistically significant," the investigators said (Cochrane Database Syst. Rev. 2012 [doi:10.1002/14651858.CD006536.pub3]).
There was no increase in adverse events related to stem cell therapy, except for a few events related to G-CSF stimulation used in two small studies. Overall, "there is no evidence that the treatment is harmful," Dr. Clifford and his associates said.
In summary, intracardiac bone marrow–derived stem cell therapy may yield benefits beyond those obtained with conventional treatments such as PCI. The researchers acknowledged that this conclusion "is perhaps optimistic." But some of the trials did report improved survival, and the 13 ongoing RCTs will address that question and will be included in the next Cochrane Review update, they noted.
The Cochrane Collaboration is a nonprofit international network of health experts. Dr. Clifford and his associates reported no financial conflicts of interest.