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One microRNA regrew pig heart muscle, then killed most of them

Heart muscle cells in adult mammals almost never divide, which is why a heart attack leaves permanent scar tissue instead of new muscle.

Crescent Bioresearch9 September, 1:19 PMGabisonia et al., Nature, 2019 · International Centre for Genetic Engineering and Biotechnology, Italy2 min read

Researchers at the International Centre for Genetic Engineering and Biotechnology in Italy had already shown that microRNA-199a could push mouse heart cells back into division. They tested the same molecule, delivered by a viral vector, in pigs recovering from an induced heart attack.

One month after treatment, the pigs receiving microRNA-199a showed clearly improved heart contractility, more muscle mass, and smaller scars than untreated animals. But the viral vector kept expressing the microRNA long after that initial window, and the uncontrolled, persistent expression caused sudden fatal arrhythmias in most of the treated pigs over the following weeks.

Pigs were chosen because their heart size and physiology sit closer to a human's than a mouse's. The same molecule that regrew heart muscle also proved lethal once its dose and duration went uncontrolled, a stark demonstration that regenerative signals need to be switched off as deliberately as they are switched on. The result pushed the field toward delivery methods that can be timed or turned off.

Crescent Discovery Series cover: One microRNA regrew pig heart muscle, then killed most of them

The same signal that heals can also kill.

Source

  1. Gabisonia, K., Prosdocimo, G., Aquaro, G. D., Carlucci, L., Zentilin, L., Secco, I., Ali, H., Braga, L., Gorgodze, N., Bernini, F., Burchielli, S., Collesi, C., Zandonà, L., Sinagra, G., Piacenti, M., Zacchigna, S., Bussani, R., Recchia, F. A., & Giacca, M. (2019). MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs. Nature, 569(7756), 418–422. https://doi.org/10.1038/s41586-019-1191-6
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