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

被引:36
|
作者
Beyer, Sebastian [1 ,2 ]
Koch, Maria [2 ,3 ]
Lee, Yie Hou [2 ,4 ,5 ]
Jung, Friedrich [6 ]
Blocki, Anna [1 ,7 ]
机构
[1] Chinese Univ Hong Kong, Inst Tissue Engn & Regenerat Med, Hong Kong, Hong Kong, Peoples R China
[2] Singapore MIT Alliance Res & Technol, BioSyM Interdisciplinary Res Grp, Singapore 229899, Singapore
[3] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Ctr Regenerat Med, Kelvin Grove, Qld 4059, Australia
[4] KK Womens & Childrens Hosp, Translat Om & Biomarkers Core, KK Res Ctr, Singapore 169857, Singapore
[5] Duke NUS Med Sch, Obstet & Gynaecol Acad Clin Program, Singapore 169857, Singapore
[6] Univ Saarland, Inst Clin Hemostasiol & Transfus Med, D-66421 Homburg, Germany
[7] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong, Hong Kong, Peoples R China
基金
新加坡国家研究基金会;
关键词
wound healing; angiogenesis; in vitro model; endothelial cells; pericytes; macrophages; cytokine; sphingolipid; SPHINGOSINE; 1-PHOSPHATE; MACROPHAGES; RECRUITMENT; PERICYTES; ASSAYS; BLOOD; MCP-1;
D O I
10.3390/ijms19102913
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:11
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