Mammalian heart regenerative capacity depends on the severity of injury, found researchers who used cyroinjury on neonatal mouse hearts.
Using cryoinjury, that is damaging the heart through exposure to extreme cold in order to mimic cellular injury caused by myocardial infarction, researchers at University of Southern California found that neonatal mouse hearts can fully recover normal function following a mild injury, though fail to regenerate after a severe injury.
Senior author Ellen Lien said that using models such as zebrafish and neonatal mice that regenerate their hearts naturally, they can begin to identify important molecules that enhance heart repair.
Newborn mice have shown the capacity for heart regeneration, but it is rapidly lost by seven days after birth. Approaches to extend this regenerative capacity in a mammalian model, from the neonatal period to the juvenile or adult period, could help identify new treatment options for humans.
In addition to differences in regenerative capacity, the investigators also found an indicator of tissue fibrosis or "scarring," profibrotic marker PAI-1, was markedly elevated only after transmural injury. In both models post-injury, the cells that form heart muscle, cardiomyocytes, did not increase significantly. However, responses to cardiac injury repair in the outer layer of the heart (epicardium) and blood vessels (revascularization) - were present.
Co-author David Warburton said that if they can figure out how to activate this youthful type of myocardial regeneration program in humans, it will be a major clinical breakthrough.
The study is published online by the journal Developmental Biology.