Endothelial progenitor cells give rise to pro-angiogenic smooth muscle-like progeny

Jan-Renier A. J. Moonen, Guido Krenning, Marja G. L. Brinker, Jasper A. Koerts, Marja J. A. van Luyn, Martin C. Harmsen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

84 Citations (Scopus)

Abstract

Reciprocal plasticity exists between endothelial and mesenchymal lineages. For instance, mature endothelial cells adopt a smooth muscle-like phenotype through transforming growth factor beta-1 (TGF beta 1)-driven endothelial-to-mesenchymal transdifferentiation (EndMT). Peripheral blood contains circulating endothelial progenitor cells of which the endothelial colony-forming cells (ECFCs) harbour stem cell-like properties. Given the plasticity between endothelial and mesenchymal lineages and the stem cell-like properties of ECFCs, we hypothesized that ECFCs can give rise to smooth muscle-like progeny.

ECFCs were stimulated with TGF beta 1, after which TGF beta signalling cascades and their downstream effects were investigated. Indeed, EndMT of ECFCs resulted in smooth muscle-like progeniture. TGF beta 1-driven EndMT is mediated by ALK5 kinase activity, increased downstream Smad2 signalling, and reduced protein levels of inhibitor of DNA-binding protein 3. ECFCs lost expression of endothelial markers and endothelial anti-thrombogenic function. Simultaneously, mesenchymal marker expression was gained, cytoskeletal rearrangements occurred, and cells acquired a contractile phenotype. Transdifferentiated ECFCs were phenotypically stable and self-sustaining and, importantly, showed fibroblast growth factor-2 and angiopoietin-1-mediated pro-angiogenic paracrine properties.

Our study is the first to demonstrate that ECFCs can give rise to smooth muscle-like progeny, with potential therapeutic benefits. These findings further illustrate that ECFCs are highly plastic, which by itself has implications for therapeutical use.

Original languageEnglish
Pages (from-to)506-515
Number of pages10
JournalCardiovascular Research
Volume86
Issue number3
DOIs
Publication statusPublished - 1-Jun-2010

Keywords

  • Endothelial progenitor cells
  • Plasticity
  • Transdifferentiation
  • Smooth muscle cells
  • EndMT
  • GROWTH-FACTOR-BETA
  • TO-MESENCHYMAL TRANSITION
  • EMBRYONIC STEM-CELLS
  • IN-VITRO
  • INDUCED RECRUITMENT
  • CORD BLOOD
  • TGF-BETA
  • PDGF-B
  • DIFFERENTIATION
  • VIVO

Cite this