Regenerative Mechanisms of the Adult Injured and Failing Heart

Abstract

Many adult mammals’ organs—from the skin to skeletal muscle, bone marrow, liver, and intestine—have strong regenerative capacity. Even the heart in lower organisms has been shown to have an ability to regenerate, often observed in invertebrates such as salamander species. In recent years, some cardiac regenerative capacities have been observed in newts, salamanders, frogs, and neonatal rodents. This begs the question: What is the human heart’s potential for regeneration? Studies have firmly established that the adult mouse heart and human heart have the capacity for cardiomyocyte turnover and replacement. Increased cardiomyocyte content is expected to enhance vascular regeneration, given its role in promoting a microvascular endothelial network to provide oxygen and nutrients. Strategies to stimulate cardiac regeneration include reprogramming fibroblasts to cardiomyocytes, or converting them back to a stem cell state or to terminated lineages by forced expression. Signaling pathways and factors have been shown to modulate the capacity of cardiomyocyte proliferation. In addition, engineering strategies are being researched to either stimulate cardiac regeneration or replace lost myocardium. Examples include the use of “scaffolds” to deliver cells and the generation of sheets of cardiomyocytes for transplantation. With millions of people living with heart failure, the ability to promote new cardiomyocytes would be a life-changing therapy.