The Benefits of Repeated Mesenchymal Stem Cell Treatments to the Heart

Mesenchymal stem cells have the ability to improve the heart after a heart attack. However can repeated administrations of mesenchymal stem cells cause an increased benefit to the heart after a heart attack?

A collaborative research project between the Royal Adelaide Hospital, the University of Adelaide in South Australia, and the Mayo Clinic in Rochester, Minnesota has administered mesenchymal stem cells multiple times to rodents after a heart attack to determine if administering these stem cells multiple times after a heart attack increases the performance of the heart.

The experimental procedure was relatively straight-forward. Three groups of mice were evaluated by means of cardiac magnetic resonance imaging (MRI). Then all three were given heart attacks by tying off the left anterior descending artery. Immediately after the heart attack, two groups were injected with one million mesenchymal stem cells into the heart. The third group was injected with ProFreeze (a cryopreservation solution). One week later, a second set of heart MRIs were taken, and the first and third group of mice received injections of ProFreeze and the third group received another one million mesenchymal stem cells. All animals were given two more heart MRIs one week later and two weeks after that. One month after the initial heart attacks, the mice were euthanized and their hearts were sectioned and examined.

Those mice that did not receive injections of mesenchymal stem cells showed a precipitous drop in their heart performance. The ejection fraction (average percent of blood pumped from the heart) dropped from around 60% to about 20% and then stayed there. Those mice treated with one round of mesenchymal stem cells (MSCs) after their ejection fractions drop from 60% to about 35% after one week, and then stayed there. Those animals that received two shots of MSCs have their ejection fractions drop from around 60% to about 41%. Thus the administration of a second round of MSCs did significantly increase the performance of the heart.

The heart also shows tremendous structural improvements as a result of MSC transplantation. These improvements are even more dramatic in those mice that received two doses of MSCs. The mass of the heart and the thickness of the walls of the heart are greater in those animals that received two MSC doses, than those that received only one dose. Secondly, the size of the heart scar is smallest in those animals that received two doses of MSCs. Third, the density of blood vessels was MUCH higher in the animals that received two MSC doses. Also, the tissue far from the infarction in those animals that had received two doses of MSCs showed twice the density of blood vessels per cubic millimeter of heart tissue than those animals that had only received one injection of MSCs. Therefore, additional transplantations of MSCs increase blood vessel density, decrease the size of the heart scar and increase the thickness of the walls of the heart.

MSCs have the capacity to heal the heart after a heart attack. The degree to which they heal the heart differs from patient to patient, but additional treatments have the capacity to augment the healing capacities of these cells.  Also, in this experiment, the mice received someone else’s MSCs.  This is known as “allogeneic” transplantation, and it is an important concept, since older patients, diabetic patients, or those who have had a heart attack typically have MSCs that do not perform well.  Therefore to receive MSCs from a donor is a way around this problem.

The problem with this experiment is that it was done in mice, and they were injected directly into the heart tissue. Such a procedure is almost certainly impractical for human patients. Instead, intracoronary delivery is probably more practical, but here again, repeated releasing cells into the coronary arteries increases the risk of clogging them. Therefore, it is probably necessary to administer the second dose of MSCs some time after the first dose. To calibrate when to administer the second dose, large animal experiments will be required.

Thus, while this experiment looks interesting and hopeful, more work is required to make this usable in humans.  It does, however, establish the efficacy of repeated allogeneic MSC transplantations, which is an important feature of these experiments.