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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

by Sebastian Beyer 1,2,†, Maria Koch 2,3,†, Yie Hou Lee 2,4,5, Friedrich Jung 6 and Anna Blocki 1,7,*
1
Institute for Tissue Engineering and Regenerative Medicine, Chinese University of Hong Kong, New Territories, Hong Kong, China
2
BioSyM Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore 229899, Singapore
3
Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia
4
Translational ‘Omics and Biomarkers core, KK Research Centre, KK Women’s and Children’s Hospital, Singapore 169857, Singapore
5
Obstetrics & Gynaecology—Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
6
Institute for Clinical Hemostasiology and Transfusion Medicine, University Saarland, 66421 Homburg/Saar, Germany
7
School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, New Territories, Hong Kong, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 2913; https://doi.org/10.3390/ijms19102913
Received: 8 August 2018 / Revised: 4 September 2018 / Accepted: 16 September 2018 / Published: 25 September 2018
(This article belongs to the Special Issue Head Tissues Regeneration)
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. View Full-Text
Keywords: wound healing; angiogenesis; in vitro model; endothelial cells; pericytes; macrophages; cytokine; sphingolipid wound healing; angiogenesis; in vitro model; endothelial cells; pericytes; macrophages; cytokine; sphingolipid
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Beyer, S.; Koch, M.; Lee, Y.H.; Jung, F.; Blocki, A. 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. Int. J. Mol. Sci. 2018, 19, 2913.

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