1. Academic Validation
  2. Ascorbic acid promotes the direct conversion of mouse fibroblasts into beating cardiomyocytes

Ascorbic acid promotes the direct conversion of mouse fibroblasts into beating cardiomyocytes

  • Biochem Biophys Res Commun. 2015 Aug 7;463(4):699-705. doi: 10.1016/j.bbrc.2015.05.127.
Mahmood Talkhabi 1 Sara Pahlavan 2 Nasser Aghdami 3 Hossein Baharvand 4
Affiliations

Affiliations

  • 1 Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
  • 2 Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
  • 3 Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: Nasser.Aghdami@RoyanInstitute.org.
  • 4 Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran. Electronic address: Baharvand@RoyanInstitute.org.
Abstract

Recent advances in the direct conversion of fibroblasts to cardiomyocytes suggest this process as a novel promising approach for cardiac cell-based therapies. Here, by screening the effects of 10 candidate small molecules along with transient overexpression of Yamanaka factors, we show ascorbic acid (AA), also known as vitamin C, enhances reprogramming of mouse fibroblasts into beating cardiomyocytes. Immunostaining and gene expression analyses for pluripotency and cardiac lineage markers confirmed beating patches were derived from non-cardiac lineage cells without passing through a pluripotent intermediate. Further analysis revealed that AA also increased the size of the beating areas and the number of cardiac progenitors. Immunostaining for cardiac markers, as well as electrophysiological analysis confirmed the functionality of directly converted cardiomyocytes. These results illustrate the importance of AA in direct conversion of fibroblasts to cardiomyocytes and may open new insights into future biomedical applications for induced cardiomyocytes.

Keywords

Ascorbic acid; Cardiomyocytes; Direct conversion; Fibroblasts; Small molecules.

Figures
Products