Conversion of human fibroblasts to angioblast-like progenitor cells
Résumé
Lineage conversion of one somatic cell type to another is an attractive approach for generating specific human cell types. Lineage conversion can be direct, in the absence of proliferation and multipotent progenitor generation, or indirect, by the generation of expandable multipotent progenitor states. We report the development of a reprogramming methodology in which cells transition through a plastic intermediate state, induced by brief exposure to reprogramming factors, followed by differentiation. We use this approach to convert human fibroblasts to mesodermal progenitor cells, including by non-integrative approaches. These progenitor cells demonstrated bipotent differentiation potential and could generate endothelial and smooth muscle lineages. Differentiated endothelial cells exhibited neo-angiogenesis and anastomosis in vivo. This methodology for indirect lineage conversion to angioblast-like cells adds to the armamentarium of reprogramming approaches aimed at the study and treatment of ischemic pathologies.
Mots clés
Animals
Humans
Mice
RNA
Messenger
Stem Cells
Cell Differentiation
Cell Lineage
Cell Proliferation
Cells
Cultured
Fibroblasts
Cellular Reprogramming
Biomarkers
Blotting
Western
Cell Movement
Endothelium
Vascular
Flow Cytometry
Fluorescent Antibody Technique
Myocytes
Smooth Muscle
Neovascularization
Physiologic
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction