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SELECTBIO Conferences Circulating Biomarkers and Extracellular Vesicles Europe 2024

Circulating Biomarkers and Extracellular Vesicles Europe 2024 Agenda



Integrating Microphysiological Systems and Extracellular Vesicle-Based Technologies to Advance Regenerative Medicine

Danilo Tagle, Associate Director for Special Initiatives, National Institutes of Health

Microphysiological systems are microfluidic cell culture chips capable of recapitulating key functional aspects of physiological human tissue and organ response. MPS have many contexts of use including evaluation of toxicity/safety, and efficacy of promising therapeutic compounds, disease modeling of both rare and common diseases, as well as within the regenerative and precision medicine space. Extracellular vesicles (EVs) are nano-sized, membrane-enclosed carriers of bioactive lipids, protein, and nucleic acids that are used for intracellular communication. Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress and other environmental exposures and early disease pathogenesis. EVs have pleiotropic actions in physiological and pathological conditions.  EVs are commonly heterogeneous in size, ranging from 20 to 1,000 nm in diameter depending on their origin and mechanism of release, direct shedding or budding from the plasma membrane. Exosomes are vesicles with a diameter of 20–100 nm formed by the inward budding of endosomal membranes to form large multivesicular bodies (MVBs) and released extracellularly when MVBs fuse with the plasma membrane.  Exosomes have recently been studied for their potential use in therapy as a 1) targeted and non-immunogenic delivery system for drugs or biological molecules, and 2) in the maintenance of tissue homeostasis and their contribution to tissue repair and regeneration. For the past few years, MPS and EV-based technologies have been combined within the regenerative medicine space to find safer, more efficacious patient therapies, as well as to probe for non-invasive diagnostic biomarkers. Combination of these technologies could potentially help address a key drug development challenge, i.e., on-target delivery without off-tissue toxicity by delivering therapeutics (small molecules, macromolecules, nucleic acids, etc.) via EVs that only act at the diseased tissue, regardless of whether a target is expressed elsewhere. This presentation will summarize NIH-funded activities in exploring the therapeutic applications of exosomes along with application of new experimental models, including organ-on-chip (OOC) systems and in vitro approaches to extend findings.