Current Insights And Advancements In Models Of Vascular Malformations: Emerging Biomarkers And Therapeutic Strategies
Yareli R. Carcamo-Bahena, BS, Maham Rahimi, MD, PhD, Alan Lumsden, MD, Carly Sue Filgueira, PhD.
Houston Methodist Research Institute, Houston, TX, USA.
OBJECTIVE: Arteriovenous malformations (AVMs) are defects of the circulatory system that can arise during development or can be acquired at any stage after birth. Our objective was to survey various models used to study AVMs ranging from in silico, in vitro, and in vivo and highlight the advantages or limitations for their use in research.
METHODS : A literature search generated 158 articles ranging from 1953-2021 for AVM and models written in English. Developing reliable AVM models are important for training endovascular therapeutic procedures, applying interventions, and testing outcomes of new therapeutics, devices, and materials. We illustrate various AVM models and compose a list of relevant histological stains and biomarkers researchers have successfully used to characterize malformations and assess changes due to progression or intervention.
RESULTS : Various considerations should be made when choosing a particular AVM model, as some animal species have large differences with humans in their cardiac contractile kinetics and heart rates, which can affect induction and differences in experimental outcome. Since the AVM location should closely resemble the human hemodynamic and pathophysiologic environment for comparative assessments, choosing an appropriate model, induction approach, and site are all important parameters to consider. Notably, our literature review provides evidence that pre-operative patient imaging can aid in the generation of 3D printed AVM models, which can prove useful for patient consultation, surgical planning, and resident training. We also describe the identification of certain markers shown to aid in the diagnosis and monitoring of progression or regression of vascular malformations. Finally, we report that lesions can be successful treated by multimodality therapy with combinations of endovascular embolization, radiosurgery, and surgical resection (including robotic-assisted procedures).
CONCLUSIONS: We propose that animals which contain a rete can offer abundant tissue and blood sampling, and maintain compatibility with human healthcare procedures, equipment, imaging modalities, and devices, such as porcine, are excellent candidates for study. We highlight recent successes in the deployment of novel non-adhesive liquid embolics, that are rapidly accelerating the field as they provide ease of use for the operator, maintain occlusion, and prevent recanalization for successful resection to minimize intraoperative complications.
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