Many researchers are exploring the therapeutic utility of microRNAs involved in fundamental cellular processes such as replication. These molecules act to regulate the processes of gene expression, determining how much of specific proteins are produced from their genetic blueprints, and when. Protein amounts are the switches and dials of cellular operation, and delivering microRNAs into cells is one possible way to steer cells into useful behavior - through the sheer complexity of the cell makes identifying the right tools to use quite difficult, and any given microRNA may produce quite sweeping changes, only few of which are helpful in any given context. Nonetheless, as illustrated here, there are some possible paths forward towards near future applications of microRNA delivery in regenerative medicine.
Once the heart is fully formed, the cells that make up heart muscle, known as cardiomyocytes, have very limited ability to reproduce themselves. After a heart attack, cardiomyocytes die off; unable to make new ones, the heart instead forms scar tissue. Over time, this can set people up for heart failure. New work advances the possibility of reviving the heart's regenerative capacities using microRNAs - small molecules that regulate gene function and are abundant in developing hearts. Researchers had earlier identified a family of microRNAs called miR-17-92 that regulates proliferation of cardiomyocytes. In the new work, they show two family members, miR-19a and miR-19b, to be particularly potent and potentially good candidates for treating heart attack.
Researchers tested the microRNAs delivered two different ways. One method gave them to mice directly, coated with lipids to help them slip inside cells. The other method put the microRNAs into a gene therapy vector designed to target the heart. Injected into mice after a heart attack - either directly into the heart or systemically - miR-19a/b provided both immediate and long-term protection. In the early phase, the first 10 days after heart attack, the microRNAs reduced the acute cell death and suppressed the inflammatory immune response that exacerbates cardiac damage. Tests showed that these microRNAs inhibited multiple genes involved in these processes. Longer-term, the treated hearts had more healthy tissue, less dead or scarred tissue and improved contractility, as evidenced by increased left-ventricular fractional shortening on echocardiography. Dilated cardiomyopathy - a stretching and thinning of the heart muscle that ultimately weakens the heart - was also reduced.