Establishment of safe and efficient cardiac reprogramming methods by controlling intracellular metabolism and histone modification.
Description: Although induced pluripotent stem (iPS) cell-based cardiac regeneration therapy has been expected, safety, costs, and duration of iPS cell derivation are considered as barriers against the clinical application. To overcome these problems, we modified the reprogramming process and created cardiac myocytes directly from fibroblasts rapidly and efficiently with few risks of tumorigenesis. Cardiac myocytes were induced from four factor-mediated reprogramming fibroblasts, while these cells are not susceptible to iPS cell formation. Global gene expression analysis and metabolome analysis revealed that these reprogramming cells seem to be early mesodermal cells including cardiac progenitors but not iPS progenitor cells. In addition, this cardiac reprogramming is promoted by activation of aerobic metabolism and chromatin-modifying enzymes. The results above may contribute to establishment of the novel strategy for safe and efficient cardiac regeneration therapy.
Amount: ¥16,380,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (B)
Start date: 2016-04-01
End date: 2020-03-31
Investigator: Teruhisa KAWAMURA
Institution: Ritsumeikan University
Funded outputs count: 2
Funder award ID: 16H04725
OpenAlex ID: G3475036699