MiRNAs to Regenerate the Heart

Abstract

### Study Hypothesis MicroRNAs (miRNAs) are small nucleic acid products that simultaneously modulate expression levels of several different genes by partial complementation, leading to posttranscriptional regulation. Among their functions, miRNAs have been shown to regulate cardiac development and differentiation. During heart development, immature cardiomyocytes proliferate actively to accommodate increasing heart size and function; however, this proliferation is abruptly abrogated shortly after birth, leaving the heart with a limited regenerative capacity insufficient to replace substantial amounts of tissue lost after injury. In this article, Eulalio et al hypothesize that neonatal proliferation capacity can be reactivated in adult cardiomyocytes by the exogenous administration of selected miRNAs, leading to cardiac repair. ### How Was the Hypothesis Tested? The authors used a synthetic whole-genome human miRNA library to induce individual expression of miRNAs in neonatal cardiomyocytes. To assess the effect of the miRNA mimics, they immunostained transfected cells for cardiac-specific proteins together with markers of DNA synthesis and proliferation. High-content fluorescence microscopy enabled quantification of proliferating cardiomyocytes and selection of the miRNAs with the highest potential to induce cell cycle reentry. To ensure that DNA replication led to nuclear division (karyokinesis) and cytoplasm division (cytokinesis), characteristic markers for late mitosis and …