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Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration

Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its...

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Autores principales: Balli, Martina, Vitali, Francesca, Janiszewski, Adrian, Caluwé, Ellen, Cortés-Calabuig, Alvaro, Carpentier, Sebastien, Duelen, Robin, Ronzoni, Flavio, Marcelis, Lukas, Bosisio, Francesca Maria, Bellazzi, Riccardo, Luttun, Aernout, De Angelis, Maria G. Cusella, Ceccarelli, Gabriele, Lluis, Frederic, Sampaolesi, Maurilio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206041/
https://www.ncbi.nlm.nih.gov/pubmed/31654035
http://dx.doi.org/10.1038/s41418-019-0433-3
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author Balli, Martina
Vitali, Francesca
Janiszewski, Adrian
Caluwé, Ellen
Cortés-Calabuig, Alvaro
Carpentier, Sebastien
Duelen, Robin
Ronzoni, Flavio
Marcelis, Lukas
Bosisio, Francesca Maria
Bellazzi, Riccardo
Luttun, Aernout
De Angelis, Maria G. Cusella
Ceccarelli, Gabriele
Lluis, Frederic
Sampaolesi, Maurilio
author_facet Balli, Martina
Vitali, Francesca
Janiszewski, Adrian
Caluwé, Ellen
Cortés-Calabuig, Alvaro
Carpentier, Sebastien
Duelen, Robin
Ronzoni, Flavio
Marcelis, Lukas
Bosisio, Francesca Maria
Bellazzi, Riccardo
Luttun, Aernout
De Angelis, Maria G. Cusella
Ceccarelli, Gabriele
Lluis, Frederic
Sampaolesi, Maurilio
author_sort Balli, Martina
collection PubMed
description Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that AMG improves skin re-epithelialization by accelerating the migration of fibroblasts and keratinocytes. More specifically, AMG-treated wounds showed improvement of indispensable events associated with successful wound healing such as granulation tissue formation, organized collagen content, and newly formed blood vessels. We demonstrate that AMG is enriched with a pool of WH-associated growth factors that may provide the starting signal for a faster endogenous wound healing response. This work links the increased cell migration rate to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which is followed by an increase in matrix metalloproteinase expression and their extracellular enzymatic activity. Overall we reveal the AMG-mediated wound healing transcriptional signature and shed light on the AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process. In this way, we present a framework for future improvements in AMG therapy for skin tissue regeneration applications.
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spelling pubmed-72060412020-05-08 Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration Balli, Martina Vitali, Francesca Janiszewski, Adrian Caluwé, Ellen Cortés-Calabuig, Alvaro Carpentier, Sebastien Duelen, Robin Ronzoni, Flavio Marcelis, Lukas Bosisio, Francesca Maria Bellazzi, Riccardo Luttun, Aernout De Angelis, Maria G. Cusella Ceccarelli, Gabriele Lluis, Frederic Sampaolesi, Maurilio Cell Death Differ Article Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that AMG improves skin re-epithelialization by accelerating the migration of fibroblasts and keratinocytes. More specifically, AMG-treated wounds showed improvement of indispensable events associated with successful wound healing such as granulation tissue formation, organized collagen content, and newly formed blood vessels. We demonstrate that AMG is enriched with a pool of WH-associated growth factors that may provide the starting signal for a faster endogenous wound healing response. This work links the increased cell migration rate to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which is followed by an increase in matrix metalloproteinase expression and their extracellular enzymatic activity. Overall we reveal the AMG-mediated wound healing transcriptional signature and shed light on the AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process. In this way, we present a framework for future improvements in AMG therapy for skin tissue regeneration applications. Nature Publishing Group UK 2019-10-25 2020-05 /pmc/articles/PMC7206041/ /pubmed/31654035 http://dx.doi.org/10.1038/s41418-019-0433-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Balli, Martina
Vitali, Francesca
Janiszewski, Adrian
Caluwé, Ellen
Cortés-Calabuig, Alvaro
Carpentier, Sebastien
Duelen, Robin
Ronzoni, Flavio
Marcelis, Lukas
Bosisio, Francesca Maria
Bellazzi, Riccardo
Luttun, Aernout
De Angelis, Maria G. Cusella
Ceccarelli, Gabriele
Lluis, Frederic
Sampaolesi, Maurilio
Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
title Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
title_full Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
title_fullStr Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
title_full_unstemmed Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
title_short Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
title_sort autologous micrograft accelerates endogenous wound healing response through erk-induced cell migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206041/
https://www.ncbi.nlm.nih.gov/pubmed/31654035
http://dx.doi.org/10.1038/s41418-019-0433-3
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