Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells

Zhaocheng Zhang; Felipe Nör; Min Oh; Carolina Cucco; Songtao Shi; Jacques E Nör

doi:10.1002/stem.2334

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Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells

Journal article

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Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells

Zhaocheng Zhang, Felipe Nör, Min Oh, Carolina Cucco, Songtao Shi and Jacques E Nör

Stem cells (Dayton, Ohio), Vol.34(6), pp.1576-1587

06/2016

DOI: 10.1002/stem.2334

PMCID: PMC5338744

PMID: 26866635

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Abstract

Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/β-catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, β-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/β-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587.

Laminin - pharmacology

Mesenchymal Stromal Cells - drug effects

Neovascularization, Physiologic - drug effects

Gene Silencing - drug effects

Endothelial Cells - metabolism

Humans

Dental Pulp - cytology

Mesenchymal Stromal Cells - metabolism

Glycogen Synthase Kinase 3 beta - antagonists & inhibitors

Mice, SCID

Glycogen Synthase Kinase 3 beta - metabolism

beta Catenin - metabolism

Gene Knockdown Techniques

Mesenchymal Stromal Cells - cytology

Animals

Wnt Signaling Pathway - drug effects

Proteoglycans - pharmacology

Cell Differentiation - drug effects

Endothelial Cells - cytology

HEK293 Cells

Collagen - pharmacology

Vascular Endothelial Growth Factor A - pharmacology

Drug Combinations

Endothelial Cells - drug effects

Details

Title: Subtitle: Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells
Creators: Zhaocheng Zhang - Department of Cariology, Restorative Sciences and Endodontics, Angiogenesis Research Laboratory, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
Felipe Nör - Department of Cariology, Restorative Sciences and Endodontics, Angiogenesis Research Laboratory, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
Min Oh - Department of Cariology, Restorative Sciences and Endodontics, Angiogenesis Research Laboratory, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
Carolina Cucco - Department of Cariology, Restorative Sciences and Endodontics, Angiogenesis Research Laboratory, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
Songtao Shi - Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA
Jacques E Nör - Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA
Resource Type: Journal article
Publication Details: Stem cells (Dayton, Ohio), Vol.34(6), pp.1576-1587
DOI: 10.1002/stem.2334
PMID: 26866635
PMCID: PMC5338744
NLM abbreviation: Stem Cells
ISSN: 1066-5099
eISSN: 1549-4918
Publisher: United States
Grant note: F30 DE025471 / NIDCR NIH HHS R01 DE021410 / NIDCR NIH HHS
Language: English
Date published: 06/2016
Academic Unit: Endodontics
Record Identifier: 9984065720802771

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