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A New Approach to Promote Heart Tissue Regeneration

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Injuries to the heart, such as after a heart attack, never fully heal due to a low level of cardiac muscle cell (cardiomyocytes) proliferation in adult mammals.

A team of researchers led by Ed Morrisey, PhD at the University of Pennsylvania has now shown that a subset of RNA molecules, called microRNAs, is important for cardiomyocyte cell proliferation during development and is sufficient to induce proliferation in cardiomyocytes in the adult heart.

The team found that the loss of the microRNA cluster miR302-367 in mice led to decreased cardiomyocyte cell proliferation during development. In contrast, increased expression of the microRNA cluster in adult hearts led to a reactivation of proliferation in the normally non-reproducing adult cardiomyocytes. 

Heart System

In studies performed on mice with experimental myocardial infarctions, it was shown that re-expressing these microRNA reactivated the cell cycle in cardiomyocytes resulting in reduced scar formation and an increased number of heart muscle cells.

One major issue that arose however was that the prolonged expression of these microRNA caused the heart muscle cells to not differentiate and therefore become less functional. Thus, it was actually harmful to leave the microRNA active.

To circumvent this issue, the team created mimics – synthetic microRNA with a short half-life. This transient treatment plan allowed for the proliferation of cardiomycotes, but only for a short time, so that the negative effects of prolonged expression could not begin.

“The next stage in this study is to determine whether miRNA mimics will work in a larger animal model and to collaborate with bioengineers to create a local delivery system for the heart, rather than giving it systemically,” notes Morrisey.

Original story from Penn Medicine: Source

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