Administration of selected short non-expressing RNA molecules (miRNAs) can stimulate the growth of new heart muscle cells. How these new cardiomyocytes integrate and function within the existing heart is not well understood. We will address these questions using advanced 3D tissue imaging methodologies to support the development and clinical translation of novel regenerative therapies.
Target discoveryIn depth
Cardiac regeneration after myocardial infarction (MI) can be achieved by the therapeutic administration of selected miRNAs that stimulate cardiomyocyte proliferation in different model organisms. While this is exciting, several questions remain outstanding and need to be answered before considering clinical translation. What is the structure of the new myocardium in response to proliferative stimulation? How do cardiomyocytes (CM) integrate in this site? What is the structure of collagen in the area and nerves and the vasculature? This project is aimed at addressing these questions by using advanced tissue imaging approaches to reconstruct regenerated mouse hearts at high-resolution.
The use 3D tissue clearing methodologies, which permit optical clearing and 3D reconstruction of entire heart at high-resolution, will assist us to detect the morphology of the cardiac muscle, the distribution of collagen and the orientation of CMs, along with the detection of specific structural features at sub-cellular level, such as the distribution of connexins and nerve buttons. This study will define the structural features of regenerated myocardium in response to miRNA-induced cardiomyocyte proliferation and comprehensively correlate the structural data to each heart’s function.
Further reading
Eulalio, A., Mano, M., Ferro, M. et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature 492, 376–381 (2012). https://doi.org/10.1038/nature11739