Polish Study Shows Stable Improvements Two Years After Heart Stem Cell Transplant


Stem cell treatments for heart attacks can improve heart function after a heart attack. This has been repeated shown in laboratory animals and human trials have also established the efficacy of bone marrow-based heart treatments. Despite these successes, there are some indications that the improvements wrought by bone marrow stem cell transplants into the heart are not stable, and the functional increases caused by it are transient.

To determine is functional improvements in the heart are transient or stable, Jaroslaw Kaspzak and his colleagues at the Medical University of Lodz, Poland have published a study in which they treated 60 heart attack patients and then tracked them for two years. Their study was published in the journal Kardiologia Polska, which, fortunately, is in English, since I do not read Polish.

In this study, 60 heart attack patients were treated with primary angioplasty and randomly assigned to two groups. The first group consisted of 40 patients who were treated with standard care, and bone marrow stem cell transplants.  The bone marrow cells were harvested 3-11 days after the heart attack. The bone marrow cells were administered to the heart by means of intracoronary catheters (over the wire balloon catheter) very near to the area of the infarct (the area in the heart damaged by the heart attack).  The second group of 20 patients were treated with standard care.  All patients were subjected to echocardiography before treatment and 1, 3, 6, 12, and 24 months after treatment.  Additionally, the percentages of patients who experienced subsequent heart attacks, admission to the hospital for heart failure, or revascularization, was tabulated two years after the treatment.

Just after the heart attack, the heart function of both groups was essentially the same.  The fraction of blood pumped from the heart (ejection fraction) in the treated group was 35% ± 6% and 33% ± 7% in the control group (normal is 55% – 70%).  The volume of blood left in the heart after it contracts (end systolic volume) was 95 milliliters ± 39 milliliters in the treated group and 99 milliliters ± 49 milliliters in the control group (normal is 50-60 milliliters).  The amount of blood in the heart after it fills (end diastolic volume) was 149 ± 48 milliliters in the treated group and 151 ± 65 milliliters in the control group (normal is 120-130 milliliters).  The end diastolic volume  (EDV) is a measure of the firmness of the heart walls.  A damaged heart is not as firm and its flaccid walls expand greatly and take up more volume, which puts further strain upon the heart.  Thus a DECREASE in the EDV is an indication of improvement in the heart.  Nevertheless, it is clear that before the treatment regimes were instigated, the average medical conditions of the two groups was essentially the same, at least when it comes to the heart.

The results of each treatment strategy are rather telling. The ejection fraction in the control group increased 3.7% one moth after the heart attack, 4.7% by 6 months, 4.8% at 12 months, and 4.7% at 24 months.  This this group saw its greatest increase six months after the heart attack and although this increase was stable, it was modest at best.  The bone marrow-treated group, however, saw an average ejection fraction increase of 7.1% after one month, 9.3% at 6 months, 11.0% after one year, and 10% after two years.  Thus the bone marrow-treated group not only showed a much faster and more robust increase in injection fraction, but an increase that was sustained two years after the procedure.  Also, the treated group saw half the percentage of deaths due to cardiac events (5%) than that observed in the control group (10%).  The percentage of hospitalizations for heart failure in the treated group (3%) was 20% of that seen in the control group (15%).  The rates of revasculaizations and new heart attacks was essentially the same in both groups.

This study joins other long-term studies that have demonstrated long-term improvements in heart attack patients treated with heart infusions with bone marrow-derived stem cells.  The REPAIR-AMI clinical trial, which examined 204 heart attack patients, showed stable, long-term benefits that lasted for at least two years for those patients who had been treated with infusions of bone marrow stem cells.  Other studies have not found no significant differences between heart attack patients treated with standard care and those who also received bone marrow infusions.  However, there are probable explanations for many of these failures.  The ASTAMI study that failed to show significant differences between the two groups not only transplanted a lower number of cells than this present study and the successful REPAIR-AMI study.  Secondly, the negative FINCELL study used patients whose average ejection fractions were 59% ± 11%.  Clinical studies that have tested bone marrow heart infusions have established that those patients with lower ejection fractions are helped the most by them.  This is the case of the negative HEBE study; the patients with the lowest ejection fraction showed the greatest improvements relative to the control group, but these improvements were swamped out by those with higher ejection fractions that were not helped nearly as much.  Third, the meta-analysis of Martin-Rendon showed that the best time period to treat heart attack patients was 4-7 days after the heart attack.  In the HEBE study, patients received bone marrow infusions 7 days after angioplasty.  How soon after the heart attack was the angioplasty performed?  This is not reported, probably because it varied from patient to patient.  Nevertheless, this places the treatment outside the optimum established by other experiments.

Thus, once again, we see that bone marrow treatments for hearts are safe, and effective, and they convey long-term benefits to patients who receive them.  Much work remains, since only some people consistently benefit from these treatments.  Why is this the case?  Only more work will tell.

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).