Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1783416838581911552 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6506241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT lingchangying differentiatedfibrocytesassumeafunctionalmesenchymalphenotypewithregenerativepotential AT nishimotokohei differentiatedfibrocytesassumeafunctionalmesenchymalphenotypewithregenerativepotential AT rolfszach differentiatedfibrocytesassumeafunctionalmesenchymalphenotypewithregenerativepotential AT smithlloydm differentiatedfibrocytesassumeafunctionalmesenchymalphenotypewithregenerativepotential AT freybrianl differentiatedfibrocytesassumeafunctionalmesenchymalphenotypewithregenerativepotential AT welhamnathanv differentiatedfibrocytesassumeafunctionalmesenchymalphenotypewithregenerativepotential |