VEGFR2-dependent angiogenic capacity of pericyte-like dental pulp stem cells

K. Janebodin, Y. Zeng, W. Buranaphatthana, N. Ieronimakis, M. Reyes

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Dental pulp stem cells (DPSCs) have previously demonstrated potential pericyte-like topography and function. However, the mechanisms regulating their pericyte function are still unknown. In this study, murine DPSC angiogenic and pericyte function were investigated. Tie2-GFP mouse DPSCs were negative for GFP, indicating the absence of endothelial cells in DPSC cultures. Endothelial cells co-cultured with DPSCs formed more mature in vitro tube-like structures as compared with those co-cultured with bone marrow stromal cells (BMSCs). Many DPSCs were located adjacent to vascular tubes, assuming a pericyte location. Subcutaneous DPSC transplants in mice with matrigel (MG) (DPSC-MG) induced more vessel formation than BMSC-MG. Soluble Flt (sFlt), an angiogenic inhibitor that binds VEGF-A, significantly decreased the amount of blood vessels in DPSC-MG, but not in BMSC-MG. sFlt inhibited VEGFR2 and downstream ERK signaling in DPSCs. Similar to sFlt inhibition, VEGFR2 knockdown in DPSCs resulted in down-regulation of Vegfa, Vegf receptors, and EphrinB2 and decreased angiogenic induction of DPSCs in vivo. Therefore, the capacity of DPSCs to induce angiogenesis is VEGFR2-dependent. DPSCs enhance angiogenesis by secreting VEGF ligands and associating with vessels resembling pericyte-like cells. This study provides first insights into the mechanism(s) of DPSC angiogenic induction and their function as pericytes, crucial aspects for DPSC use in tissue regeneration.

Original languageEnglish (US)
Pages (from-to)524-531
Number of pages8
JournalJournal of Dental Research
Volume92
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Keywords

  • adult stem cells
  • angiogenesis
  • neovascularization
  • neural crest
  • soluble Flt
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Dentistry(all)

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