Cardiomyocytes, green, proliferating in a mouse heart after gel injection. (Credit: University of Pennsylvania)

After a heart attack, there is a dramatic loss of heart muscle cells, known as cardiomyocytes, and those that survive cannot effectively replicate. Researchers have demonstrated a new approach to restart replication: an injectable gel that slowly releases short gene sequences known as microRNAs into the heart muscle.

Though the reasons cardiomyocytes don’t regenerate aren’t fully understood, the researchers used microRNAs that target signaling pathways related to cell proliferation, and were able to inhibit some of the inherent “stop” signals that keep cardiomyocytes from replicating. This resulted in cardiomyocytes reactivating their proliferative potential.

With more heart cells dividing and reproducing, mice treated with this gel after heart attack showed improved recovery in key clinically relevant categories.

MicroRNA-based therapies have been studied in the past, but delivering the right dose to the right place has been a consistent challenge. Their short lifespan means that if patients were treated systemically, they would need to be injected frequently with large doses to ensure that a sufficient amount of microRNAs reaches their target in the heart. And because these microRNAs are designed to promote cell proliferation, there would be a risk of tumor-producing, off-target effects.

Researchers says the most important traits of this gel are that it’s shear-thinning and self-healing. Shear-thinning means it has bonds that can be broken under mechanical stress, making it more fluid and allowing it to flow through a syringe or catheter. Self-healing means that when that stress is removed, the gel’s bonds re-form, allowing it to stay in place within the heart muscle.