Bone Marrow Cell Infusions Do NOT Improve Cardiac Function After Heart Attack
For over a decade, cardiologists have been conducting trials in patients using cells extracted from the bone marrow and infusing them into the blood vessels of the heart in patients who have suffered a heart attack. This type of a procedure is not without risks. It involves multiple invasive procedures in patients who are already quite ill, because they are experiencing a major heart attack:
1) Patients with a major heart attack (also referred to as ST-elevation Myocardial Infarction or STEMI) usually undergo an immediate angiogram of the heart to treat the blockage that is causing the heart attack by impeding the blood flow. This is the standard of care for heart attack patients in the developed world.
2) Patients enrolled in an experimental cell therapy trial are then brought back for a second procedure during which bone marrow is extracted with a needle under local anesthesia.
3) The research patients then undergo another angiogram of the heart using a catheter which allows for the infusion of bone marrow cells into the heart.
The hope is that the stem cells contained within the bone marrow are able to help regenerate the heart, either by turning into heart cells (cardiomyocytes), blood vessel cells (endothelial cells) or releasing factors that protect the heart and prevent the formation of a large scar. Unfortunately, there is very limited scientific evidence that bone marrow stem cells can actually turn into functional heart cells. The trials that have been conducted so far have yielded mixed results - some show that infusing the bone marrow cells indeed improves heart function, others show that patients who just receive the standard therapy with cell infusions do just as well. Most of the trials have been quite small - often studying only 10-50 patients.
The SWISS-AMI cell therapy trial, published online on April 17, 2013 in the world's leading cardiovascular research journal Circulation, addressed this question in a randomized, controlled trial, which enrolled 200 patients who had suffered a major heart attack. The published paper is entitled "Intracoronary Injection of Bone Marrow Derived Mononuclear Cells, Early or Late after Acute Myocardial Infarction: Effects on Global Left Ventricular Function" and was conducted in Switzerland.
The researchers assigned the patients to three groups: a) Standard heart attack treatment, b) Standard heart attack treatment and infusion of bone marrow cells 5-7 days after the heart attack or c) Standard heart attack treatment and infusion of bone marrow cells 3-4 weeks after the heart attack. They assessed heart function four months later using cardiac magnetic resonance imaging, one of the best tools available to determine heart function. The results were rather disappointing: Neither of the two cell treatment groups showed any improvement in their cardiac function.
This trial had some important limitations: Even though this study enrolled 200 patients and was thus larger than most other cell therapy trials for heart attack patients, it is still a rather small study when compared to other cardiovascular studies, which routinely enroll thousands of patients. Furthermore, this study only assessed heart function after four months and it is possible that if they had waited longer, they might have seen some benefit of the cell therapy. Despite these limitations, the trial will dampen the general enthusiasm for injecting bone marrow cells into heart attack patients.
Is this study a set-back for cardiac stem cell treatments? Not really. As the authors reveal in their data analysis, most of the cells contained in the bone marrow preparation that they used for the infusion were plain old white blood cells and NOT stem cells. Actually, only 1% of the infused cells were hematopoietic stem cells (stem cells that give rise to blood cells) and there was an undisclosed percentage of other stem cell types (such as mesenchymal stem cells) contained in the infused bone marrow extract. As I point out in the accompanying editorial "Bone Marrow Tinctures for Cardiovascular Disease: Lost in Translation", using such a mixture of poorly defined cells is ill-suited to promote cardiac regeneration or repair. Therefore, this important study is not a set-back for cardiac stem cell therapy, but a well-deserved setback for injections of undefined cells, most of which are not true stem cells!
Even if the majority of infused cells had been stem cells, there is no guarantee that merely infusing them into the heart would necessarily result in the formation of new heart tissue. Regenerating heart tissue from adult stem cells requires priming or directing stem cells towards becoming heart cells and ensuring that the cells can attach and integrate into the heart, not just infusing or injecting them into the heart.
It is commendable that the journal published this negative study, because too many treatments are being marketed as "stem cell therapies" without clarifying whether the injected cells are truly efficacious. Hopefully, the results of this trial will lead to more caution when rushing to perform "stem cell treatments" in patients without carefully defining the scientific characteristics and therapeutic potential of the cells that are being used.
Link to the editorial: "Bone Marrow Tinctures for Cardiovascular Disease: Lost in Translation"
Image credit: Surgeon extracting bone marrow from a patient (Public Domain image via Wikimedia)
Surder, D., Manka, R., Lo Cicero, V., Moccetti, T., Rufibach, K., Soncin, S., Turchetto, L., Radrizzani, M., Astori, G., Schwitter, J., Erne, P., Zuber, M., Auf der Maur, C., Jamshidi, P., Gaemperli, O., Windecker, S., Moschovitis, A., Wahl, A., Buhler, I., Wyss, C., Kozerke, S., Landmesser, U., Luscher, T., & Corti, R. (2013). Intracoronary Injection of Bone Marrow Derived Mononuclear Cells, Early or Late after Acute Myocardial Infarction: Effects on Global Left Ventricular Function Four months results of the SWISS-AMI trial Circulation DOI: 10.1161/CIRCULATIONAHA.112.001035
Rehman, J. (2013). Bone Marrow Tinctures for Cardiovascular Disease: Lost in Translation Circulation DOI: 10.1161/CIRCULATIONAHA.113.002775