Platform to assess extracellular vesicles transport across the blood brain barrier
Inventors: Marsha Moses, Golnaz Morad
Invention Types: Therapeutics, Diagnostic/Prognostic
Keywords: Assay, CNS, Disease Model, Drug Delivery, Drug Discovery, Drug Screening, Method of Use, Tissue Engineering, Platform
The blood brain barrier (BBB) is a dynamic and complex structure consisting of several cell types that together form a highly selective barrier - a major limiting factor in developing diagnostic and therapeutic approaches for brain disorders. Extracellular vesicles (EVs) have recently been shown to play a role in cellular communication between the brain and the periphery, both for homeostasis and in disease processes, and are being heavily studied as a potential drug-delivery vehicle. Developing this tool has so far been limited by lack of appropriate modeling of EV transport across the BBB.
Dr. Moses’s group has previously shown that EVs can get transported through the BBB and have now developed a novel platform to assess the process and mechanism of this transport. They have modified an in vitro model of the BBB by applying specific culture conditions that enhance the tight junctions between brain endothelial cells and decrease the permeability of the barrier (Figure 1) – a feature critical to modeling the BBB and that more reliably recapitulates the native barrier. This model is then combined with a state-of-the-art labeling approach that avoids contamination by free dye, a common problem with the conventional labeling methods. The group has further developed rigorous approaches for assessment and validation of the platform, including assays to exclude paracellular transport and contamination by free labels.
Furthermore, using live imaging and histological evaluations in zebrafish and mouse models, the group confirmed the validity of in vitro findings with regard to the transport of EVs across the brain endothelium. Consistency between in vitro and in vivo findings demonstrates the high reliability of the novel presented platform for assessment of the transport of EVs across the BBB as an early tool that could facilitate the bench-to-bedside translation of EVs as potential diagnostics and therapeutics.
• Platform to evaluate EVs as therapeutics for CNS disorders.
• Platform for diagnostic and prognostic evaluation of CNS disorders
• Robust and reliable model of EV transport across blood brain barrier
• Accurate tracking of EV transport across blood brain barrier
Key Publications: Manuscript in preparation.
Related Publications: The following abstracts have been presented for this work:
1. Breast cancer-derived extracellular vesicles modulate the activity of signaling pathways in the brain microenvironment. International Society for Extracellular Vesicles Annual Meeting, 2018, Barcelona, Spain [Oral presentation]
2. Using proteomics profiling to elucidate the interactions of breast cancer-derived exosomes with the blood brain barrier. American Association for Cancer Research Annual Meeting, 2018, Chicago, IL [Poster presentation]
3. The role of breast cancer-derived exosomes in brain metastasis. American Association for Cancer Research Annual Meeting, 2017, Washington, D.C. [Poster presentation]
IPStatus: Pat. Pend.