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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Angiopoietin-1, Biomarkers, Cell Lineage, Cell Transdifferentiation, Cells, Cultured, Cytoskeleton, Endothelial Cells, Fetal Blood, Fibroblast Growth Factor 2, Humans, Inhibitor of Differentiation Proteins, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Neoplasm Proteins, Neovascularization, Physiologic, Paracrine Communication, Phenotype, Protein-Serine-Threonine Kinases, Receptor, Transforming Growth Factor-beta Type I, Receptors, Transforming Growth Factor beta, Signal Transduction, Smad2 Protein, Stem Cells, Time Factors, Transforming Growth Factor beta1, Vasoconstriction.
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Do endothelial progenitor cells give rise to pro-angiogenic smooth muscle-like progeny? Context: Reciprocal plasticity exists between endothelial and mesenchymal lineages. For instance, mature endothelial cells adopt a smooth muscle-like phenotype through transforming growth factor beta-1 (TGFbeta1)-driven endothelial-to-mesenchymal transdifferentiation (EndMT). Peripheral blood contains circulating endothelial progenitor cells of which the endothelial colony-forming cells (ECFCs) harbour stem cell-like properties. Given the plasticity between endothelial and mesenchymal lineages and the stem cell-like properties of ECFCs, we hypothesized that ECFCs can give rise to smooth muscle-like progeny. ECFCs were stimulated with TGFbeta1, after which TGFbeta signalling cascades and their downstream effects were investigated. Indeed, EndMT of ECFCs resulted in smooth muscle-like progeniture. TGFbeta1-driven EndMT is mediated by ALK5 kinase activity, increased downstream Smad2 signalling, and reduced protein levels of inhibitor of DNA-binding protein 3. ECFCs lost expression of endothelial markers and endothelial anti-thrombogenic function. Simultaneously, mesenchymal marker expression was gained, cytoskeletal rearrangements occurred, and cells acquired a contractile phenotype. Transdifferentiated ECFCs were phenotypically stable and self-sustaining and, importantly, showed fibroblast growth factor-2 and angiopoietin-1-mediated pro-angiogenic paracrine properties.
assistant
Our study is the first to demonstrate that ECFCs can give rise to smooth muscle-like progeny, with potential therapeutic benefits. These findings further illustrate that ECFCs are highly plastic, which by itself has implications for therapeutical use. Final Decision: yes