Cardiac Progenitor Cell–Derived Extracellular Vesicles Reduce Infarct Size and Associate with Increased Cardiovascular Cell Proliferation

Janita A. Maring, Kirsten Lodder, Emma Mol, Vera Verhage, Karien C. Wiesmeijer, Calinda K.E. Dingenouts, Asja T. Moerkamp, Janine C. Deddens, Pieter Vader, Anke M. Smits, Joost P.G. Sluijter, Marie José Goumans*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Downloads (Pure)

Abstract

Cell transplantation studies have shown that injection of progenitor cells can improve cardiac function after myocardial infarction (MI). Transplantation of human cardiac progenitor cells (hCPCs) results in an increased ejection fraction, but survival and integration are low. Therefore, paracrine factors including extracellular vesicles (EVs) are likely to contribute to the beneficial effects. We investigated the contribution of EVs by transplanting hCPCs with reduced EV secretion. Interestingly, these hCPCs were unable to reduce infarct size post-MI. Moreover, injection of hCPC-EVs did significantly reduce infarct size. Analysis of EV uptake showed cardiomyocytes and endothelial cells primarily positive and a higher Ki67 expression in these cell types. Yes-associated protein (YAP), a proliferation marker associated with Ki67, was also increased in the entire infarcted area. In summary, our data suggest that EV secretion is the driving force behind the short-term beneficial effect of hCPC transplantation on cardiac recovery after MI.

Original languageEnglish
Pages (from-to)5-17
Number of pages13
JournalJournal of Cardiovascular Translational Research
Volume12
Issue number1
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Angiogenesis
  • Cardiac progenitor cells
  • Cardiomyocytes
  • Endoglin
  • Extracellular vesicles
  • Myocardial infarction
  • Proliferation
  • Myocytes, Cardiac/metabolism
  • Cell Proliferation
  • Humans
  • Male
  • Endoglin/metabolism
  • Extracellular Vesicles/metabolism
  • Transcription Factors/metabolism
  • Myocardial Infarction/metabolism
  • rab GTP-Binding Proteins/genetics
  • Disease Models, Animal
  • Cells, Cultured
  • Mice, SCID
  • Adaptor Proteins, Signal Transducing/metabolism
  • Ki-67 Antigen/metabolism
  • rab27 GTP-Binding Proteins/genetics
  • Regeneration
  • Animals
  • Stem Cell Transplantation/methods
  • Mice, Inbred NOD

Fingerprint

Dive into the research topics of 'Cardiac Progenitor Cell–Derived Extracellular Vesicles Reduce Infarct Size and Associate with Increased Cardiovascular Cell Proliferation'. Together they form a unique fingerprint.

Cite this