Related Experiment Video
Updated: Sep 3, 2025
Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Cardiomyocytes induced from hiPSCs by well-defined compounds have therapeutic potential in heart failure by secreting
Hongmei Li1,2, Fenfang Wu3, Guangrui Huang1
1School of Life Science, Beijing University of Chinese Medicine, Beijing, China.
Insights
Optimally induced human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show enhanced therapeutic effects for heart failure by promoting repair and reducing cardiac dysfunction. These cells secrete PDGF-BB, activating the PI3K/Akt pathway for improved myocardial repair.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show promise for heart failure treatment.
- The immaturity of hiPSC-CMs and their secreted factors limit clinical benefits.
- Key paracrine factors involved in hiPSC-CMs-mediated cardiac repair are largely unknown.
Purpose of the Study:
- To establish an optimized system for generating functional hiPSC-CMs for cell therapy.
- To investigate the therapeutic effects and underlying mechanisms of these optimized hiPSC-CMs in a heart failure model.
- To identify key secreted factors and signaling pathways involved in cardiac repair.
Main Methods:
- Development of a saponin-positive compound-induced system for hiPSC-CM generation.
- Transplantation of optimized hiPSC-CMs into heart failure mouse models.
- Assessment of cardiac function, remodeling, angiogenesis, and cell survival.
- Analysis of secreted factors, particularly PDGF-BB, and downstream signaling pathways (PI3K/Akt).
Main Results:
- Optimized hiPSC-CMs transplantation attenuated cardiac remodeling and dysfunction in heart failure mice.
- Beneficial effects included reduced cardiomyocyte death and increased angiogenesis.
- Optimized hiPSC-CMs secreted abundant PDGF-BB, which mimicked reparative effects and activated the PI3K/Akt pathway.
- PDGF-BB neutralization inhibited the therapeutic effects, confirming its crucial role.
Conclusions:
- Optimized hiPSC-CMs promote myocardial repair via paracrine action, primarily through PDGF-BB secretion.
- The PDGF-BB/PI3K/Akt pathway mediates the beneficial effects of optimized hiPSC-CMs on cardiac remodeling and function.
- Optimized hiPSC-CMs represent a promising cell therapy for clinical applications in heart failure treatment.
Abstract:
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.
More Related Videos
09:23Generation, High-Throughput Screening, and Biobanking of Human-Induced Pluripotent Stem Cell-Derived Cardiac Spheroids
Published on: March 10, 2023
08:00Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
Published on: July 10, 2019