Open AccessWnt/β‐Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells
Author(s) -
Zhang Zhaocheng,
Nör Felipe,
Oh Min,
Cucco Carolina,
Shi Songtao,
Nör Jacques E.
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2334
Subject(s) - vasculogenesis , mesenchymal stem cell , biology , stem cell , wnt signaling pathway , microbiology and biotechnology , adult stem cell , induced stem cells , stem cell transplantation for articular cartilage repair , endothelial stem cell , cancer research , progenitor cell , signal transduction , in vitro , biochemistry
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. S tem C ells 2016;34:1576–1587