Abstract Number: PB2169
Meeting: ISTH 2020 Congress
Background: Cancer patients have a 4- to 7- fold increased risk of venous thromboembolism (VTE). Cancer-associated thrombosis is a major cause of morbidity and one of the main causes of death in these patients. Currently, mouse models are used to study the mechanisms involved in this pathology and to allow preclinical testing. However, mouse models cannot be used to properly mimic the human pathology, since mice do not develop thrombosis spontaneously. The biological mechanisms involved in cancer-associated thrombosis are still unknown.
Aims: Develop a humanized organ-on-a-chip model to study cancer-associated thrombosis.
Methods: The OrganoPlate Graft (Mimetas BV) was used as a platform to mimic a cancer-associated thrombosis environment. Human umbilical vein endothelial cells (HUVECs) were isolated, expanded and seeded in the perfusion channels from the OrganoPlate Graft. In parallel, spheroids of HT-29 human colorectal cancer cell line were generated using 10,000 cells/well which were seeded in non-adherent round bottom 96-wells plates. After 3-4 days of HUVEC and spheroid seeding, pro-angiogenic growth factors were added to the perfusion channel, and/or colorectal cancer spheroids were added to the graft chamber. After another 3 days of co-culture, the model was assessed for cell morphology, barrier permeability, and thrombin formation.
Results: Preliminary data showed that the addition of pro-angiogenic growth factors or colorectal cancer spheroids increased the permeability of the endothelial barrier. Pre-incubation of endothelial cells with TNF-α induced thrombin formation after the addition of citrated human plasma and calcium. Moreover, there was more thrombin formation when pro-angiogenic growth factors were added in comparison with conditions that included colorectal cancer spheroid and control.
Conclusions: Our data showed that the cancer-associated thrombosis model is a promising model to study this pathology in vitro incorporating a 3D environment in a microfluidic system. This work was funded by Health~Holland.
To cite this abstract in AMA style:Rondon AMR, Laghmani EH, Stam W, van Duinen V, Queiroz K, Vulto P, van Zonneveld AJ, Versteeg H. Developing an ex vivo Method to Study Thrombosis in Cancer Patients: Cancer-associated Thrombosis-on-a-Chip [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/developing-an-ex-vivo-method-to-study-thrombosis-in-cancer-patients-cancer-associated-thrombosis-on-a-chip/. Accessed December 6, 2021.
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