Abstract Number: LPB0096
Meeting: ISTH 2021 Congress
Background: Ischemic heart disease is the leading cause of death worldwide. Most cases are caused by atherosclerosis. Erosion of this plaque triggers unwanted blood clotting which blocks the blood supply to the heart, triggering heart attacks. This process is currently principally studied in animal models.
Aims: To create a tissue-engineered neointima as an alternative to current animal models and assess its effect on primary and secondary haemostasis.
Methods: THP-1 derived foam cells were cultured within collagen hydrogels and triggered to differentiate into foam cells by treatment with lipopolysaccharide, IFN-γ, and oxidised low-density lipoprotein. Prothrombin times were measured to assess the procoagulant activity of the tissue-engineered neointimal constructs using platelet-poor plasma prepared from blood of healthy medication-free volunteers. Platelet aggregation was assessed using light transmission aggregometry. Tissue factor activity was measured using the fluorogenic substrate SN-17.
Results: This novel in vitro neo-intima tissue can trigger rapid coagulation of human plasma due to the presence of significant tissue factor activity. Prothrombin times were 87.5 ± 8.4s , 158.3 ± 12.7s and 376.6 ± 28.1s for gels containing foams cell, M1 cells or no additional cells respectively (n = 6 ; P < 0.05). Collagen hydrogels containing THP-1 derived foam cells samples had significantly greater tissue factor activity compared to cell-free hydrogels or M1 macrophage-containing hydrogels. The cell-free collagen hydrogel was found not to trigger platelet aggregation, whilst both the M1- and foam cell-containing hydrogels were found to initiate a slow, but reproducible, platelet activation.
Conclusions: Our tissue-engineered neointimal model can recreate the pro-thrombotic potential of human atherosclerotic plaques. This could form the basis for a novel in vitro 3D model of human atherosclerosis to replace current animal models.
To cite this abstract in AMA style:Echrish J, Yang Y, Harper A. Development of a 3D Tissue-engineered Neointimal Model as an Alternative to Animal Models of Human Atherosclerosis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/development-of-a-3d-tissue-engineered-neointimal-model-as-an-alternative-to-animal-models-of-human-atherosclerosis/. Accessed August 19, 2022.
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