Conversion of human fibroblasts to angioblast-like progenitor cells.

Journal: 
Nat Methods
Publication Year: 
2012
Authors: 
Leo Kurian
Ignacio Sancho-Martinez
Emmanuel Nivet
Aitor Aguirre
Krystal Moon
Caroline Pendaries
Cecile Volle-Challier
Francoise Bono
Jean-Marc Herbert
Julian Pulecio
Yun Xia
Mo Li
Nuria Montserrat
Sergio Ruiz
Ilir Dubova
Concepcion Rodriguez
Ahmet M Denli
Francesca S Boscolo
Rathi D Thiagarajan
Fred H Gage
Jeanne F Loring
Louise C Laurent
Juan Carlos Izpisua Belmonte
PubMed link: 
23202434
Public Summary: 
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.
Scientific 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.