News Releases & Research Results Efficient induction of cardiomyocytes using a soft scaffold for establishment of a new method for cardiac regeneration

The results of research conducted by Professor Masaki Ieda and Assistant Professor Taketaro Sadahiro of Department of Cardiology, Faculty of Medicine, University of Tsukuba, and others.

• As a method for cardiac regeneration, a virus vector (*1) was used to induce conversion of cardiac fibroblasts to cardiomyocytes (cardiomyocyte induction). The efficiency of the method was found to be dependent on the softness of the extracellular matrix (*2) used as a scaffold.
  (*1) It infects the host cell, enters the host genome (DNA), and facilitates expression of the gene of interest. In this way, it serves as a carrier for gene transduction into the cell.
  (*2) It is a sugar-protein complex that is present outside the cells and it serves as a physical scaffold for the cells.
• Specifically, the efficiency of cardiomyocyte induction was drastically improved using a culture dish covered with extracellular matrix, with softness equivalent to that of the living heart, which enabled efficient induction of mature cardiomyocytes. In addition, by using the soft extracellular matrix, the efficiency of Sendai-virus (*3)-mediated cardiomyocyte induction, considered to be the most efficient method for cardiomyocyte induction at present, improved by two times and the induction efficiency of beating mature cardiomyocytes increased up to 15%.
  (*3) A virus vector that can facilitate gene expression in the host cell cytoplasm after infecting the host cells without entering the host genome (DNA), resulting in no damage to the genome itself.
• The research results may contribute to not only elucidation of the mechanism of cardiomyocyte induction, but also to clinical application of regenerative treatment for various heart diseases characterized by replacement of solid fibrous tissue in the heart (e.g., myocardial infarction and dilated cardiomyopathy).

This project was conducted with the support of Research Center Network for Realization of Regenerative Medicine and Advanced Research and Development Programs for Medical Innovation by AMED.

The research results were published online in Stem Cell Reports on August 28.

KurotsuS., et al. Soft Matrix Promotes Cardiac Reprogramming via Inhibition of YAP/TAZ and Suppression of Fibroblast Signatures Stem Cell Reports
DOI：10.1016/j.stemcr.2020.07.022