Conversion of human fibroblasts to angioblast-like progenitor cells

authors

• Kurian Leo
• Sancho-Martinez Ignacio
• Nivet Emmanuel
• Aguirre Aitor
• Moon Krystal
• Pendaries Caroline
• Volle-Challier Cecile
• Bono Francoise
• Herbert Jean-Marc
• Pulecio Julian
• Xia Yun
• Li Mo
• Montserrat Nuria
• Ruiz Sergio
• Dubova Ilir
• Rodriguez Concepcion
• Denli Ahmet M.
• Boscolo Francesca S.
• Thiagarajan Rathi D.
• Gage Fred H.
• Loring Jeanne F.
• Laurent Louise C.
• Izpisua Belmonte Juan Carlos

keywords

• 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

abstract

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.

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