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Establishing Human and Canine Xenograft Murine Osteosarcoma Models for Application of Focused Ultrasound Ablation
Alayna N Hay1,2, Alex Simon3, Lauren N Ruger3
1Department of Small Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA.
Abstract:
Background: Osteosarcoma (OS) is the most commonly occurring type of bone cancer in both humans and canines. The survival outcomes for OS patients have not improved significantly in decades. A novel and innovative treatment option that is currently under investigation for OS in the veterinary field is the focused ultrasound ablation modality, histotripsy. Histotripsy is a non-thermal, non-invasive, non-ionizing ablation modality that destroys tissue through generation of acoustic cavitation. Objective: In the current study, we sought to investigate the utility of an orthotropic OS xenograft murine model for characterization of chronic ablative and clinical outcomes post-histotripsy ablation. Method: Given the high comparative relevance of canine to human OS, histotripsy was delivered to orthotopic OS tumors in both human and canine xenograft murine models. Results: Histotripsy improved limb function in tumor-bearing mice compared to untreated tumor bearing mice. The results of this study demonstrated the utility of the orthotopic OS xenograft murine model for histotripsy-based preclinical studies. Conclusions: The current study is the first published investigation for the use of an orthotopic xenograft murine model for the development of histotripsy ablation for OS. The developmental process of the model, technical limitations, and future directions are discussed.
Insights
Histotripsy, a novel non-invasive treatment, improved limb function in mice with osteosarcoma (OS). This study validates an orthotopic xenograft model for preclinical histotripsy research in OS.
Area of Science:
- Oncology
- Biomedical Engineering
- Preclinical Research
Background:
- Osteosarcoma (OS) is a prevalent bone cancer in humans and canines with stagnant survival rates.
- Histotripsy, a non-invasive focused ultrasound ablation technique, shows promise for OS treatment.
- Acoustic cavitation is the mechanism by which histotripsy ablates tissue.
Purpose of the Study:
- To evaluate an orthotopic OS xenograft murine model for preclinical histotripsy studies.
- To characterize chronic ablative and clinical outcomes following histotripsy in OS models.
- To assess the translational relevance of canine and human OS xenografts for histotripsy development.
Main Methods:
- Histotripsy was applied to orthotopic OS tumors in human and canine xenograft murine models.
- The study utilized xenograft models due to the high comparative relevance of canine OS to human OS.
- Functional outcomes and ablative effects were assessed post-treatment.
Main Results:
- Histotripsy demonstrated improved limb function in tumor-bearing mice compared to controls.
- The orthotopic OS xenograft murine model proved effective for preclinical histotripsy investigations.
- The study successfully characterized outcomes following histotripsy ablation.
Conclusions:
- This research pioneers the use of orthotopic xenograft models for histotripsy development in OS.
- The study discusses the model's development, technical challenges, and future research directions.
- Findings support the potential of histotripsy as an innovative treatment for osteosarcoma.
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