Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip.
Heleen H T MiddelkampHuub J WeenerT GensheimerK VermeulL E de HeusHugo J AlbersAlbert van den BergAndries D van der MeerPublished in: Biomedical microdevices (2023)
Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells - a phenomenon known as 'thromboinflammation'. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular in vitro model in drug development for early atherosclerosis or aspects of other vascular diseases.
Keyphrases
- endothelial cells
- high throughput
- circulating tumor cells
- induced apoptosis
- oxidative stress
- wound healing
- high glucose
- cell cycle arrest
- stem cells
- single cell
- magnetic resonance imaging
- cell adhesion
- high resolution
- computed tomography
- coronary artery
- mesenchymal stem cells
- fatty acid
- pulmonary embolism
- cell death
- bone marrow
- peripheral blood
- cell proliferation
- cell therapy
- mass spectrometry
- hyaluronic acid
- current status
- diabetic rats
- platelet rich plasma