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An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase

Successful vascularization is essential in wound healing, the histo-integration of biomaterials, and other aspects of regenerative medicine. We developed a functional in vitro assay to dissect the complex processes directing angiogenesis during wound healing, whereby vascular cell spheroids were ind...

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Detalles Bibliográficos
Autores principales: Beyer, Sebastian, Koch, Maria, Lee, Yie Hou, Jung, Friedrich, Blocki, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213254/
https://www.ncbi.nlm.nih.gov/pubmed/30257508
http://dx.doi.org/10.3390/ijms19102913
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author Beyer, Sebastian
Koch, Maria
Lee, Yie Hou
Jung, Friedrich
Blocki, Anna
author_facet Beyer, Sebastian
Koch, Maria
Lee, Yie Hou
Jung, Friedrich
Blocki, Anna
author_sort Beyer, Sebastian
collection PubMed
description Successful vascularization is essential in wound healing, the histo-integration of biomaterials, and other aspects of regenerative medicine. We developed a functional in vitro assay to dissect the complex processes directing angiogenesis during wound healing, whereby vascular cell spheroids were induced to sprout in the presence of classically (M1) or alternatively (M2) activated macrophages. This simulated a microenvironment, in which sprouting cells were exposed to the inflammatory or proliferation phases of wound healing, respectively. We showed that M1 macrophages induced single-cell migration of endothelial cells and pericytes. In contrast, M2 macrophages augmented endothelial sprouting, suggesting that vascular cells infiltrate the wound bed during the inflammatory phase and extensive angiogenesis is initiated upon a switch to a predominance of M2. Interestingly, M1 and M2 shared a pro-angiogenic secretome, whereas pro-inflammatory cytokines were solely secreted by M1. These results suggested that acute inflammatory factors act as key inducers of vascular cell infiltration and as key negative regulators of angiogenesis, whereas pro-angiogenic factors are present throughout early wound healing. This points to inflammatory factors as key targets to modulate angiogenesis. The here-established wound healing assay represents a useful tool to investigate the effect of biomaterials and factors on angiogenesis during wound healing.
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spelling pubmed-62132542018-11-14 An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase Beyer, Sebastian Koch, Maria Lee, Yie Hou Jung, Friedrich Blocki, Anna Int J Mol Sci Communication Successful vascularization is essential in wound healing, the histo-integration of biomaterials, and other aspects of regenerative medicine. We developed a functional in vitro assay to dissect the complex processes directing angiogenesis during wound healing, whereby vascular cell spheroids were induced to sprout in the presence of classically (M1) or alternatively (M2) activated macrophages. This simulated a microenvironment, in which sprouting cells were exposed to the inflammatory or proliferation phases of wound healing, respectively. We showed that M1 macrophages induced single-cell migration of endothelial cells and pericytes. In contrast, M2 macrophages augmented endothelial sprouting, suggesting that vascular cells infiltrate the wound bed during the inflammatory phase and extensive angiogenesis is initiated upon a switch to a predominance of M2. Interestingly, M1 and M2 shared a pro-angiogenic secretome, whereas pro-inflammatory cytokines were solely secreted by M1. These results suggested that acute inflammatory factors act as key inducers of vascular cell infiltration and as key negative regulators of angiogenesis, whereas pro-angiogenic factors are present throughout early wound healing. This points to inflammatory factors as key targets to modulate angiogenesis. The here-established wound healing assay represents a useful tool to investigate the effect of biomaterials and factors on angiogenesis during wound healing. MDPI 2018-09-25 /pmc/articles/PMC6213254/ /pubmed/30257508 http://dx.doi.org/10.3390/ijms19102913 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Beyer, Sebastian
Koch, Maria
Lee, Yie Hou
Jung, Friedrich
Blocki, Anna
An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase
title An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase
title_full An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase
title_fullStr An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase
title_full_unstemmed An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase
title_short An In Vitro Model of Angiogenesis during Wound Healing Provides Insights into the Complex Role of Cells and Factors in the Inflammatory and Proliferation Phase
title_sort in vitro model of angiogenesis during wound healing provides insights into the complex role of cells and factors in the inflammatory and proliferation phase
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213254/
https://www.ncbi.nlm.nih.gov/pubmed/30257508
http://dx.doi.org/10.3390/ijms19102913
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