A double blow to a heart attack
In a study on large animals, scientists from the University of Alabama, USA, have shown that injection of heart muscle cells derived from induced human pluripotent stem cells (hiPSCs) that overexpress cyclin-D2, one of the family of proteins involved in cell division, can lead to recovery after myocardial infarction. The researchers used pigs because they are anatomically and physiologically closest to humans, and the results obtained have high clinical significance for the treatment of humans.
A difficult problem for bioengineers is the inability of the heart to regenerate after a heart attack, when part of its muscle wall dies. The presence of a non-functioning site leads to a compensatory increase in the load on neighboring cells, and this, in turn, can cause a life-threatening increase in the heart.
Specialists from laboratories around the world are striving to create new myocardial tissue – by applying a patch with cardiomyocytes or injecting them – to replace the damaged muscle. In addition, they tried to stimulate the division of their own cardiomyocytes located near the infarction zone.
The new study combined the benefits of each approach. To do this, after an experimental heart attack, about 30 million bioengineered human cardiomyocytes were injected into the heart tissue near the infarction zone, which were grown from hiPSCs. In these cells, the expression of cyclin-D2, one of the proteins involved in division, is increased.
Compared with natural human cardiomyocytes, cardiomyocytes synthesizing cyclin-D2 showed an increased ability to repair heart tissue. In pigs, they began dividing immediately after injection, after four weeks the size of the necrosis zone decreased, and the functional parameters of the heart improved.
Interestingly, the cyclin-D2–expressing cardiomyocytes not only divided themselves, but also stimulated the proliferation of heart muscle cells around the infarction zone, and also triggered angiogenesis - the growth of new blood vessels.
The ability of transplanted cyclin-D2-expressing cardiomyocytes to stimulate the proliferation of their own heart cells may be related to the paracrine signaling pathway, a type of cellular communication in which a cell produces a signal that induces changes in neighboring cells. It is carried out by means of exosomes.
The researchers found that the exosomes that were found near cyclin-D2 cardiomyocytes contained microRNAs that stimulated proliferation.
In addition, cardiomyocytes under the influence of these exosomes became more resistant to apoptosis. Exosomes of cyclin-D2-expressing cardiomyocytes also induced proliferation of other cell types, including human umbilical vein endotheliocytes, human vascular smooth muscle cells and 7-day rat cardiomyocytes.
Thus, the combination of the direct action of cyclin-D2 and the proliferative effect of bioengineered cardiomyocytes mediated by exosomes may become a promising new strategy for enhancing the regeneration of heart cells after myocardial infarction.
Article M.Zhao et al. Cyclin D2 Overexpression Enhances the Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Repair in a Swine Model of Myocardial Infarction published in the journal Circulation.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to UAB News: Heart attack recovery aided by injecting heart muscle cells that overexpress cyclin D2.