An injectable gel could change the ability of contractile heart muscle cells to regenerate after myocardial infarction (MI), according to researchers at the University of Pennsylvania.
Edward Morrisey, MD, lead author of the study and the namesake of Penn’s Morrisey lab, which studies signaling pathways involved in heart and lung development, worked with a team to produce and test this innovative gel in an effort to improve the lifespan of heart patients. Since, after a heart attack, mammals’ hearts are unable to properly regenerate cardiomyocytes, cardiac patients are left with a heart that pumps less blood that it should, increasing mortality rates.
The researchers tested the new substance in three groups of mice: normal, healthy mice; “Confetti” mice who are genetically engineered to have individual cardiomyocytes that randomly express one of four fluorescent proteins; and mice who had induced heart attacks.
Within days of injection, the first group of mice saw increased cardiomyocyte production in their heart tissue. After inducing MI in the Confetti mice, Morrisey and colleagues found cardiomyocytes were growing and clustering. The third cohort showed improved recovery rates, as well, with minor increases in heart size and significant differences in ejection fraction.
It’s unknown exactly what keeps cardiomyocytes from reproducing after myocardial infarction, Morrisey et al. wrote, but the gel they created is able to inhibit those “stop” signals by targeting signaling pathways related to cell proliferation. To achieve this, the substance slowly releases microRNA sequences into the heart muscle.
The gel was specifically designed for this purpose, the authors wrote, so it’s both shear-thinning and self-healing, meaning its tough bonds can be broken under mechanical stress, allowing increased fluidity, and its bonds are able to reform after being exposed to stress.
Though it was successful in preliminary trials with rodent models, the researchers quickly identified the gel’s shortcomings.
“Biologic drugs turn over very fast,” Morrisey said in a release from Penn. “The microRNAs that we used last less than eight hours in the bloodstream, so having a high local concentration has strong advantages.”
Because of this, they wrote, large amounts of the substance would have to be injected frequently into the heart muscle to achieve optimum results.
Since the results of this study, published in Nature Biomedical Engineering this week, were so positive, the authors said in the Penn release they’re moving to the next step of this project—testing the microRNA gel in vitro and in pig hearts, which are more humanlike than rodents’.
“We’re seeing a change in approaches for regenerative medicine, using alternatives to stem cell delivery,” co-author Jason Burdick, PhD, said. “Here, instead of introducing new cells that can have their own delivery challenges, we’re simply turning on repair mechanisms in cells that survive injury in the heart and other tissues.”