Mesenchymal Precursor Cells Reduce Cardiac Scar in Heart Failure Patients


Heart failure is a life-limiting condition that affects over 40 million patients worldwide. Fortunately, people who suffer from heart disease now may have new hope. A new study suggests that damaged tissue can be regenerated by means of a stem cell treatment that was injected into the heart during surgery.

This small-scale study was published in the Journal of Cardiovascular Translational Research. It treated and then followed 11 patients who, during coronary artery bypass graft surgery, had stem cells directly injected into their heart muscle near the site of the tissue scars that had resulted from previous heart attacks.

The most common cause of heart failure is “Ischemic cardiomyopathy” or ICM. ICM occurs when the heart has enlarged to such a degree that the vasculature can no longer supply the heart with adequate blood. ICM can also result from multiple sites of blockage in the coronary arteries of the heart that prevent adequate circulation in the heart.

In this study, researchers delivered a novel stem cell mesenchymal precursor cell type (iMP) during coronary artery bypass surgery (CABG) in patients with ICM whose ejection fractions were below 40%. The iMP cells are derived from what seem to be very young mesenchymal stem cells that lack the typical cell-surface proteins of mesenchymal stem cells. The cells have the ability to form a variety of mesodermal-derived tissues. Also, these cells suppress immunological rejection by the patient’s body, and therefore, they can be implanted into a patient’s body, even though their tissue types do not match. Therefore, these cells can not only be expanded in culture, but can also potentially differentiate into heart-based cell types, including heart muscle and blood vessels.

This study was a phase IIa safety study that was NOT placebo-controlled, double-blinded. It enrolled 11 patients, all of whom underwent scintigraphy imaging (SPECT) before their surgery. SPECT is an effect means to detect “hibernating myocardium” that does not properly contract. Hibernating myocardium is not suitable for iMP implantation.

During the CABG surgery, iMP cells were implanted in the heart muscle (intramyocardially). Stem cells were injected into predefined areas that were viable and close to infarct areas that usually showed poor vascularization. Such areas, because of their poor vascularization could not be treated with grafting because of their poor target vessel quality.

After surgery, SPECT imaging was used to identify changes in scar area. Fortunately, Intramyocardial implantation of iMP cells with CABG was safe. The huge surprise came with the reduction of the heart scar. Subjects showed a 40% reduction in the size of scarred tissue. Remember that heart scars form after a heart attack, and can increase the chances of further heart failure. This scarring, however, was previously thought to be permanent and irreversible. The patients also showed improved myocardial contractility and perfusion of nonrevascularized areas of the heart in addition to significant reduction in left ventricular scar area at 12 months after treatment.

“Quite frankly it was a big surprise to find the area of scar in the damaged heart got smaller,” said Prof Stephen Westaby from John Radcliffe hospital in Oxford, who undertook the research at AHEPA university hospital in Thessaloniki, Greece, with Kryiakos Anastasiadis and Polychronis Antonitsis.

Clinical improvement was correlated with significant improvements in quality of life at 6 months after the treatment all patients.

Jeremy Pearson, the associate medical director at the British Heart Foundation (BHF), said: “This very small study suggests that targeted injection into the heart of carefully prepared cells from a healthy donor during bypass surgery, is safe. It is difficult to be sure that the cells had a beneficial effect because all patients were undergoing bypass surgery at the same time, which would usually improve heart function.

“A controlled trial with substantially more patients is needed to determine whether injection of these types of cells proves any more effective than previous attempts to improve heart function in this way, which have so far largely failed.”

Dr. Westaby noted that improvements in the health of their patients were partly a result of the heart bypass surgery. However, he added that the next study would include a control group who will undergo CABG but not receive stem cell treatment, in order to measure exactly what impact the treatment has.

“These patients came out of heart failure partly due to the bypass grafts of course, but we think it was partly due to the fact that they had a smaller area of scar [as a result of the stem cell treatment]. Certainly this finding of scar being reduced is quite fascinating,” he said.

These results suggest that the delivery of iMP cells can induce regeneration of heart muscle and other heart tissues in patients with ischemic heart failure.

This paper was published: Anastasiadis, K., Antonitsis, P., Westaby, S. et al. J. of Cardiovasc. Trans. Res. (2016) 9: 202. doi:10.1007/s12265-016-9686-0.

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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).