PlumX Metrics
Embed PlumX Metrics

Cardiomyocytes induced from hiPSCs by well-defined compounds have therapeutic potential in heart failure by secreting PDGF-BB

Signal Transduction and Targeted Therapy, ISSN: 2059-3635, Vol: 7, Issue: 1, Page: 253
2022
  • 8
    Citations
  • 0
    Usage
  • 12
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Recent studies have suggested that transplant of hiPS-CMs is a promising approach for treating heart failure. However, the optimally clinical benefits have been hampered by the immature nature of the hiPS-CMs, and the hiPS-CMs-secreted proteins contributing to the repair of cardiomyocytes remain largely unidentified. Here, we established a saponin compound optimally induced system to generate hiPS-CMs with stable functional attributes in vitro and transplanted in heart failure mice. Our study showed enhanced therapeutic effects of optimally induced hiPS-CMs by attenuating cardiac remodeling and dysfunction, these beneficial effects were concomitant with reduced cardiomyocytes death and increased angiogenesis. Moreover, the optimally induced hiPS-CMs could gathering to the injured heart and secret an abundant PDGF-BB. The reparative effect of the optimally induced hiPS-CMs in the hypoxia-injured HCMs was mimicked by PDGF-BB but inhibited by PDGF-BB neutralizing antibody, which was accompanied by the changed expression of p-PI3K and p-Akt proteins. It is highly possible that the PI3K/Akt pathway is regulated by the PDGF-BB secreted from the compound induced hiPS-CMs to achieve a longer lasting myocardial repair effect compared with the standard induced hiPS-CMs. Taken together, our data strongly implicate that the compound induced hiPS-CMs promote the recovery of injured hearts via paracrine action. In this process, the paracrine factor PDGF-BB derived from the compound induced hiPS-CMs reduces isoproterenol-induced adverse cardiac remodeling, which is associated with improved cardiac function, and these effects are mediated by the PI3K/Akt pathway, suggesting that the optimally induced hiPS-CMs may serve as a new promising cell therapy for clinical applications.

Bibliographic Details

Li, Hongmei; Wu, Fenfang; Huang, Guangrui; Wu, Di; Wang, Ting; Wang, Xiashuang; Wang, Kai; Feng, Yuyin; Xu, Anlong

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know