Departmental Papers (Dental)
Date of this Version
Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that post-natal 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 (DPSC) or deciduous teeth (SHED) as models of post-natal 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, 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 post-natal 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 post-natal mesenchymal stem cells.
This is the pre-peer reviewed version of the following article: [Zhang, Z., Nör, F., Oh, M., Cucco, C., Shi, S., & Nör, J. E. (2016). Wnt/β-catenin signaling determines the vasculogenic fate of postnatal mesenchymal stem cells: Wnt/β-catenin signaling and vasculogenesis. Stem Cells, 34(6), 1576-1587. doi:10.1002/stem.2334], which has been published in final form at [http://dx.doi.org/10.1002/stem.2334]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Vasculogenesis, Angiogenesis, Dental pulp stem cells, Multipotency, Self-renewal, Tissue engineering
Zhang, Z., Nor, F., Oh, M., Cucco, C., Shi, S., & Nör, J. E. (2016). Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Post-Natal Mesenchymal Stem Cells. Stem Cells, 34 (6), 1576-1587. http://dx.doi.org/10.1002/stem.2334
Date Posted: 01 March 2022
This document has been peer reviewed.