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Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure
The formation of healthy vascularized granulation tissue is essential for rapid wound closure and the prevention of chronic wounds in humans, yet how endothelial cells and fibroblasts coordinate during this process has been difficult to study. Here, we have developed an in vitro system that reveals...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AIP Publishing LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817247/ https://www.ncbi.nlm.nih.gov/pubmed/33511324 http://dx.doi.org/10.1063/5.0028651 |
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author | Tefft, Juliann B. Chen, Christopher S. Eyckmans, Jeroen |
author_facet | Tefft, Juliann B. Chen, Christopher S. Eyckmans, Jeroen |
author_sort | Tefft, Juliann B. |
collection | PubMed |
description | The formation of healthy vascularized granulation tissue is essential for rapid wound closure and the prevention of chronic wounds in humans, yet how endothelial cells and fibroblasts coordinate during this process has been difficult to study. Here, we have developed an in vitro system that reveals how human endothelial and stromal cells in a 3D matrix respond during wound healing and granulation tissue formation. By creating incisions in engineered cultures composed of human umbilical vein endothelial cells and human lung fibroblasts embedded within a 3D matrix, we observed that these tissues are able to close the wound within approximately 4 days. Live tracking of cells during wound closure revealed that the process is mediated primarily by fibroblasts. The fibroblasts migrate circumferentially around the wound edge during early phases of healing, while contracting the wound. The fibroblast-derived matrix is, then, deposited into the void, facilitating fibroblast migration toward the wound center and filling of the void. Interestingly, the endothelial cells remain at the periphery of the wound rather than actively sprouting into the healing region to restore the vascular network. This study captures the dynamics of endothelial and fibroblast-mediated closure of three-dimensional wounds, which results in the repopulation of the wound with the cell-derived extracellular matrix representative of early granulation tissue, thus presenting a model for future studies to investigate factors regulating vascularized granulation tissue formation. |
format | Online Article Text |
id | pubmed-7817247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AIP Publishing LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-78172472021-01-27 Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure Tefft, Juliann B. Chen, Christopher S. Eyckmans, Jeroen APL Bioeng Articles The formation of healthy vascularized granulation tissue is essential for rapid wound closure and the prevention of chronic wounds in humans, yet how endothelial cells and fibroblasts coordinate during this process has been difficult to study. Here, we have developed an in vitro system that reveals how human endothelial and stromal cells in a 3D matrix respond during wound healing and granulation tissue formation. By creating incisions in engineered cultures composed of human umbilical vein endothelial cells and human lung fibroblasts embedded within a 3D matrix, we observed that these tissues are able to close the wound within approximately 4 days. Live tracking of cells during wound closure revealed that the process is mediated primarily by fibroblasts. The fibroblasts migrate circumferentially around the wound edge during early phases of healing, while contracting the wound. The fibroblast-derived matrix is, then, deposited into the void, facilitating fibroblast migration toward the wound center and filling of the void. Interestingly, the endothelial cells remain at the periphery of the wound rather than actively sprouting into the healing region to restore the vascular network. This study captures the dynamics of endothelial and fibroblast-mediated closure of three-dimensional wounds, which results in the repopulation of the wound with the cell-derived extracellular matrix representative of early granulation tissue, thus presenting a model for future studies to investigate factors regulating vascularized granulation tissue formation. AIP Publishing LLC 2021-01-19 /pmc/articles/PMC7817247/ /pubmed/33511324 http://dx.doi.org/10.1063/5.0028651 Text en © 2021 Author(s). 2473-2877/2021/5(1)/016102/10 All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Articles Tefft, Juliann B. Chen, Christopher S. Eyckmans, Jeroen Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure |
title | Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure |
title_full | Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure |
title_fullStr | Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure |
title_full_unstemmed | Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure |
title_short | Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure |
title_sort | reconstituting the dynamics of endothelial cells and fibroblasts in wound closure |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817247/ https://www.ncbi.nlm.nih.gov/pubmed/33511324 http://dx.doi.org/10.1063/5.0028651 |
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