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Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential

Fibrocytes (FCs) are hematopoietic lineage cells that migrate to sites of injury, transition to a mesenchymal phenotype, and help to mediate wound repair. Despite their relevance to human fibrotic disorders, there are few data characterizing basic FC biology. Herein, using proteomic, bioenergetic, a...

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Autores principales: Ling, Changying, Nishimoto, Kohei, Rolfs, Zach, Smith, Lloyd M., Frey, Brian L., Welham, Nathan V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506241/
https://www.ncbi.nlm.nih.gov/pubmed/31086819
http://dx.doi.org/10.1126/sciadv.aav7384
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author Ling, Changying
Nishimoto, Kohei
Rolfs, Zach
Smith, Lloyd M.
Frey, Brian L.
Welham, Nathan V.
author_facet Ling, Changying
Nishimoto, Kohei
Rolfs, Zach
Smith, Lloyd M.
Frey, Brian L.
Welham, Nathan V.
author_sort Ling, Changying
collection PubMed
description Fibrocytes (FCs) are hematopoietic lineage cells that migrate to sites of injury, transition to a mesenchymal phenotype, and help to mediate wound repair. Despite their relevance to human fibrotic disorders, there are few data characterizing basic FC biology. Herein, using proteomic, bioenergetic, and bioengineering techniques, we conducted deep phenotypic characterization of differentiating and mature FCs. Differentiation was associated with metabolic reprogramming that favored oxidative phosphorylation. Mature FCs had distinct proteomes compared to classic mesenchymal cells, formed functional stromae that supported epithelial maturation during in vitro organotypic culture, and exhibited in vivo survival and self-tolerance as connective tissue isografts. In an in vitro scratch assay, FCs promoted fibroblast migration and wound closure by paracrine signaling via the chemokine CXCL8 (interleukin-8). These findings characterize important aspects of FC differentiation and show that, in addition to their role in wound healing, FCs hold potential as an easily isolated autologous cell source for regenerative medicine.
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spelling pubmed-65062412019-05-13 Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential Ling, Changying Nishimoto, Kohei Rolfs, Zach Smith, Lloyd M. Frey, Brian L. Welham, Nathan V. Sci Adv Research Articles Fibrocytes (FCs) are hematopoietic lineage cells that migrate to sites of injury, transition to a mesenchymal phenotype, and help to mediate wound repair. Despite their relevance to human fibrotic disorders, there are few data characterizing basic FC biology. Herein, using proteomic, bioenergetic, and bioengineering techniques, we conducted deep phenotypic characterization of differentiating and mature FCs. Differentiation was associated with metabolic reprogramming that favored oxidative phosphorylation. Mature FCs had distinct proteomes compared to classic mesenchymal cells, formed functional stromae that supported epithelial maturation during in vitro organotypic culture, and exhibited in vivo survival and self-tolerance as connective tissue isografts. In an in vitro scratch assay, FCs promoted fibroblast migration and wound closure by paracrine signaling via the chemokine CXCL8 (interleukin-8). These findings characterize important aspects of FC differentiation and show that, in addition to their role in wound healing, FCs hold potential as an easily isolated autologous cell source for regenerative medicine. American Association for the Advancement of Science 2019-05-08 /pmc/articles/PMC6506241/ /pubmed/31086819 http://dx.doi.org/10.1126/sciadv.aav7384 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Ling, Changying
Nishimoto, Kohei
Rolfs, Zach
Smith, Lloyd M.
Frey, Brian L.
Welham, Nathan V.
Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential
title Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential
title_full Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential
title_fullStr Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential
title_full_unstemmed Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential
title_short Differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential
title_sort differentiated fibrocytes assume a functional mesenchymal phenotype with regenerative potential
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506241/
https://www.ncbi.nlm.nih.gov/pubmed/31086819
http://dx.doi.org/10.1126/sciadv.aav7384
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