Conversion of vascular endothelial cells into multipotent stem-like cells
- 21 November 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 16 (12), 1400-1406
- https://doi.org/10.1038/nm.2252
Abstract
Under certain conditions, endothelial cells can transform into mesenchymal cell types, a process known as endothelial-to-mesenchymal transition. Damian Medici et al. now provide evidence that this type of transition contributes to the generation of the ossified lesions of individuals with fibrodysplasia ossificans progressiva. Experiments in mice and in cultured endothelial cells indicate that activation of the ALK2 receptor in endothelial cells endows them with the ability to differentiate into a number of cell types. Mesenchymal stem cells can give rise to several cell types, but varying results depending on isolation methods and tissue source have led to controversies about their usefulness in clinical medicine. Here we show that vascular endothelial cells can transform into multipotent stem-like cells by an activin-like kinase-2 (ALK2) receptor–dependent mechanism. In lesions from individuals with fibrodysplasia ossificans progressiva (FOP), a disease in which heterotopic ossification occurs as a result of activating ALK2 mutations, or from transgenic mice expressing constitutively active ALK2, chondrocytes and osteoblasts expressed endothelial markers. Lineage tracing of heterotopic ossification in mice using a Tie2-Cre construct also suggested an endothelial origin of these cell types. Expression of constitutively active ALK2 in endothelial cells caused endothelial-to-mesenchymal transition and acquisition of a stem cell–like phenotype. Similar results were obtained by treatment of untransfected endothelial cells with the ligands transforming growth factor-β2 (TGF-β2) or bone morphogenetic protein-4 (BMP4) in an ALK2-dependent manner. These stem-like cells could be triggered to differentiate into osteoblasts, chondrocytes or adipocytes. We suggest that conversion of endothelial cells to stem-like cells may provide a new approach to tissue engineering.Keywords
This publication has 39 references indexed in Scilit:
- The basics of epithelial-mesenchymal transitionJCI Insight, 2009
- Ligand‐specific function of transforming growth factor beta in epithelial‐mesenchymal transition in heart developmentDevelopmental Dynamics, 2009
- Fibroblasts in Kidney Fibrosis Emerge via Endothelial-to-Mesenchymal TransitionJournal of the American Society of Nephrology, 2008
- Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP)Journal of Bone and Mineral Metabolism, 2008
- Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangiomaNature Medicine, 2008
- Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP)Bone, 2008
- The role of endothelial-to-mesenchymal transition in cancer progressionBritish Journal of Cancer, 2008
- Human Pulmonary Valve Progenitor Cells Exhibit Endothelial/Mesenchymal Plasticity in Response to Vascular Endothelial Growth Factor-A and Transforming Growth Factor-β 2Circulation Research, 2006
- The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create itDevelopmental Dynamics, 2005
- Bone Morphogenetic ProteinsGrowth Factors, 2004