A novel mouse model for studying deep vein thrombosis (DVT) has emerged, showcasing significant advances over traditional methods. Researchers at Kanagawa Cancer Center, Japan, developed this model to provide insights relevant to human conditions, especially cancer-associated thrombosis (CAT), which is often poorly mirrored by existing animal experiments.
Deep vein thrombosis is the formation of blood clots within the deep veins, commonly seen in individuals with certain cancers. The risk of venous thromboembolism is heightened by various factors, impacting cancer patient outcomes. Traditional mouse models, namely the inferior vena cava ligation (IVC-L) model, involve obstruction of blood flow, which fails to replicate the physiological conditions of human DVT adequately. By applying ameroid constrictors (AC), this team developed the inferior vena cava hypoperfusion (IVC-H) model, intended to maintain blood flow (BF) similar to human conditions.
The innovative AC, made of hygroscopic casein, is placed around the IVC and descending aorta. The device swells with moisture, effectively constricting the vessels over time. This method allows for the observation of thrombus development over several days post-implantation, with findings evaluated using ultrasound and histological techniques.
Results were promising; the IVC-H model demonstrated reproducible thrombus formation, with size variability comparable to the IVC-L model, yet maintained blood flow—a significant improvement for therapeutic evaluations. On assessing thrombi formed at three and eight days post-AC implantation, researchers noted substantial compositional differences. Thrombi at day eight exhibited characteristics more consistent with human thrombi observed during the subacute to chronic stage of thrombosis.
“The AC model showed reproducibility with no significant difference in thrombus size variability from the traditional ligation model,” stated the authors of the article. This model bridged the gap between lab observations and human conditions, opening pathways for novel investigations focused on anticoagulant treatments and their efficacy.
Notably, as the thrombus matured over the observation period, specific histopathological transformations were evident. There was reduced fibrin content and increased collagen presence, hinting at changes reflective of prolonged thrombus age, corroborated by morphological studies on human thrombi.
The findings suggest not only a reliable model for studying DVT but also one with potential applications for research involving cancer therapeutics. “The maintained BF in this model broadened its potential use to study anticancer drug-induced DVT,” the research team noted, emphasizing its role within oncology studies.
With this model promising higher fidelity with human venous thrombosis dynamics, future research can lead to enhanced treatments and understandings of CAT. Overall, this study not only introduces practical methodologies but could also catalyze advances in therapeutic strategy developments for managing thromboembolic events.
Conclusively, the presented IVC-H model using ameroid constrictors stands as a transformative shift for DVT research, merging experimental insights closer to clinical realities and potentially re-envisioning therapeutic directions for cancer-associated coagulative complications.