Journal article
Human Embryonic Stem Cell-Derived Cardiovascular Progenitors Repair Infarcted Hearts Through Modulation of Macrophages via Activation of Signal Transducer and Activator of Transcription 6
Antioxidants & redox signaling, Vol.31(5), pp.369-386
08/10/2019
DOI: 10.1089/ars.2018.7688
PMCID: 6602123
PMID: 30854870
Abstract
Aims:
Human embryonic stem cell derived-cardiovascular progenitor cells (hESC-CVPCs) are a promising cell source for cardiac repair, while the underlying mechanisms need to be elucidated. We recently observed cardioprotective effects of human pluripotent stem cell (hPSC)-CVPCs in infarcted nonhuman primates, but their effects on inflammation during early phase of myocardial infarction (MI) and the contribution of such effect to the cardioprotection are unclear.
Results:
Injection of hESC-CVPCs into acutely infarcted myocardium significantly ameliorated the functional worsening and scar formation, concomitantly with reduced inflammatory reactions and cardiomyocyte apoptosis as well as increased vascularization. Moreover, hESC-CVPCs modulated cardiac macrophages toward a reparative phenotype in the infarcted hearts, and such modulation was further confirmed
in vitro
using human cardiovascular progenitor cell (hCVPC)-conditioned medium (hCVPC-CdM) and highly contained interleukin (IL)-4/IL-13. Furthermore, signal transducer and activator of transcription 6 (STAT6) was activated in hCVPC-CdM- and IL-4/IL-13-treated macrophages
in vitro
and in hESC-CVPC-implanted MI hearts, resulting in the polarization of macrophages toward a reparative phenotype in the post-MI hearts. However, hESC-CVPC-mediated modulation on macrophages and cardioprotection were abolished in STAT6-deficient MI mice.
Innovation:
This is the first report about the immunoregulatory role played by hESC-CVPCs in the macrophage polarization in the infarcted hearts, its importance for the infarct repair, and the underlying signaling pathway. The findings provide new insight into the mechanism of microenvironmental regulation of stem cell-based therapy during acute MI.
Conclusions:
Implantion of hESC-CVPCs during the early phase of MI promotes infarct repair
via
the modulation of macrophage polarization through secreted cytokine-mediated STAT6 activation. The findings suggest a therapeutic potential by modulating macrophage polarization during acute phase of MI.
Details
- Title: Subtitle
- Human Embryonic Stem Cell-Derived Cardiovascular Progenitors Repair Infarcted Hearts Through Modulation of Macrophages via Activation of Signal Transducer and Activator of Transcription 6
- Creators
- Jinxi Wang - Shanghai Jiao Tong UniversityMeilan Liu - Shanghai Jiao Tong UniversityQiang Wu - Center for Excellence in Molecular Cell ScienceQiang Li - Center for Excellence in Molecular Cell ScienceLing Gao - Shanghai Jiao Tong UniversityYun Jiang - Center for Excellence in Molecular Cell ScienceBoxiong Deng - Chinese Academy of SciencesWei Huang - University of Cincinnati Medical CenterWei Bi - Shanghai Jiao Tong UniversityZhongyan Chen - Center for Excellence in Molecular Cell ScienceY. Eugene Chin - Chinese Academy of SciencesChristian Paul - University of Cincinnati Medical CenterYigang Wang - University of Cincinnati Medical CenterHuang-Tian Yang - Center for Excellence in Molecular Cell Science
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.31(5), pp.369-386
- Publisher
- Mary Ann Liebert, Inc., publishers
- DOI
- 10.1089/ars.2018.7688
- PMID
- 30854870
- PMCID
- 6602123
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Language
- English
- Date published
- 08/10/2019
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984446280302771
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