Title |
Vascular Morphogenesis in the Context of Inflammation: Self-Organization in a Fibrin-Based 3D Culture System
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Published in |
Frontiers in Physiology, June 2018
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DOI | 10.3389/fphys.2018.00679 |
Pubmed ID | |
Authors |
Beate M. Rüger, Tanja Buchacher, Alexander Giurea, Bernd Kubista, Michael B. Fischer, Johannes M. Breuss |
Abstract |
Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix. Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro, and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model. Material and Methods: Synovial tissue fragments from patients with rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) were cultivated within 3D fibrin matrices for up to 4 weeks. Cellular and structural re-arrangement of the initially acellular matrix were documented by phase contrast microscopy and characterized by confocal laser-scanning microscopy of topographically intact 3D cultures and by immunohistochemistry. MSC-peripheral blood mononuclear cell (PBMC) co-cultures in the 3D fibrin system specifically addressed the influence of perivascular cell interactions to neo-vessel formation in a pro-inflammatory microenvironment. Cytokine levels in the supernatants of cultured explant tissues and co-cultures were evaluated by the Bio-Plex cytokine assay and ELISA. Results: Vascular outgrowth from the embedded tissue into the fibrin matrix was preceded by leukocyte egress from the tissue fragments. Neo-vessels originating from both the embedded sample and from clusters locally formed by emigrated mononuclear cells were consistently associated with CD45+ leukocytes. MSC and PBMC in co-culture formed vasculogenic clusters. Clusters and cells with endothelial phenotype emerging from them, were surrounded by a collagen IV scaffold. No vascular structures were observed in control 3D monocultures of PBMC or MSC. Paracrine signals released by cultured OA tissue fragments corresponded with elevated levels of granulocyte-colony stimulating factor, vascular endothelial growth factor and interleukin-6 secreted by MSC-PBMC co-cultures. Conclusion: Our results show that synovial tissue fragments with immune cell infiltrates have the potential to form new vessels in initially avascular 3D fibrin-based matrices. Cross-talk and cluster formation of MSC with immune cells within the 3D fibrin environment through self-organization and secretion of pro-angiogenic paracrine factors can support neo-vessel growth. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 33% |
Switzerland | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 5 | 18% |
Student > Master | 4 | 14% |
Professor > Associate Professor | 3 | 11% |
Student > Bachelor | 2 | 7% |
Student > Ph. D. Student | 2 | 7% |
Other | 2 | 7% |
Unknown | 10 | 36% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 4 | 14% |
Biochemistry, Genetics and Molecular Biology | 3 | 11% |
Immunology and Microbiology | 2 | 7% |
Nursing and Health Professions | 1 | 4% |
Agricultural and Biological Sciences | 1 | 4% |
Other | 4 | 14% |
Unknown | 13 | 46% |