Endothelial Colony-Forming Cells Do Not Participate to Fibrogenesis in a Bleomycin-Induced Pulmonary Fibrosis Model in Nude Mice |
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Authors: | Adeline Blandinières Thomas Gille Jérémy Sadoine Ivan Bièche Lofti Slimani Blandine Dizier Pascale Gaussem Catherine Chaussain Carole Planes Peter Dorfmüller Dominique Israël-Biet David M Smadja |
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Institution: | 1.AP-HP, European Georges Pompidou Hospital, Hematology Department ,Paris,France;2.Paris Descartes University, Sorbonne Paris Cité,Paris,France;3.Inserm UMR-S1140,Paris,France;4.AP-HP, Avicenne Hospital, Physiology Department ,Paris,France;5.Laboratory EA 2496 Orofacial Pathologies, Imaging and Biotherapies,Montrouge,France;6.Pharmacogenomics Unit, Department of Genetics,Institut Curie,Paris,France;7.Centre Chirurgical Marie Lannelongue, INSERM U999,Le Plessis Robinson,France;8.AP-HP, European Georges Pompidou Hospital, Respiratory Medicine Department ,Paris,France |
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Abstract: | Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease characterized by fibroblast proliferation, extracellular matrix deposition, destruction of pulmonary alveolar architecture and vascular remodeling. Apart pirfenidone or nintendanib that only slow down the fibrotic process, there is no curative treatment other than lung transplantation. Because cell therapy approaches have been proposed in IPF, we hypothesized that injection of endothelial colony-forming cells (ECFCs), the vasculogenic subtype of endothelial progenitor cells, could modulate fibrosis in a Nude mouse model of bleomycin induced-pulmonary fibrosis. Mice were injected with ECFCs isolated from cord blood and from peripheral blood of adult IPF patients at two time-points: during the development of the fibrosis or once the fibrosis was constituted. We assessed morbidity, weight variation, collagen deposition, lung imaging by microCT, Fulton score and microvascular density. Neither ECFCs isolated from cord blood nor from IPF patients were able to modulate fibrosis or vascular density during fibrogenesis or when fibrosis was constituted. These findings indicate that human ECFCs do not promote an adaptive regenerative response in the lung upon fibrosis or angiogenic process in the setting of bleomycin-induced pulmonary fibrosis in Nude mice. |
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