Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury

Muthukumar Gunasekaran, Rachana Mishra, Progyaparamita Saha, David Morales, Wen Chih Cheng, Arun R. Jayaraman, Jessica R. Hoffman, Lauran Davidson, Ling Chen, Aakash M. Shah, Gregory Bittle, Xuebin Fu, Antariksh Tulshyan, Mohamed Abdullah, Tami Kingsbury, Curt Civin, Peixin Yang, Michael E. Davis, Roberto Bolli, Joshua M. HareSudhish Sharma*, Sunjay Kaushal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Successful cell therapy requires cells to resist the hostile ischemic myocardium, be retained to continue secreting cardioprotective growth factors/exosomes, and resist immunological host responses. Clinically relevant stem/progenitor cells in a rodent model of acute myocardial infarction (MI) demonstrated that neonatal cardiac mesenchymal stromal cells (nMSCs) provide the most robust cardiac functional recovery. Transplanted nMSCs significantly increased the number of tissue reparative macrophages and regulatory T-cells and decreased monocyte-derived inflammatory macrophages and neutrophils in the host myocardium. mRNA microarray and single-cell analyses combined with targeted depletion studies established CD47 in nMSCs as a key molecule responsible for cell retention in the myocardium through an antiphagocytic mechanism regulated by miR34a-5p. Gain and loss-of-function studies demonstrated that miR34a-5p also regulated the production of exosomes and cardioprotective paracrine factors in the nMSC secretome. In conclusion, miR34a-5p and CD47 play an important role in determining the composition of nMSCs’ secretome and immune evasion, respectively.

Original languageEnglish (US)
Article number104656
JournaliScience
Volume25
Issue number8
DOIs
StatePublished - Aug 19 2022

Keywords

  • Cell biology
  • Molecular biology
  • Molecular medicine
  • Stem cells research

ASJC Scopus subject areas

  • General

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