Cross-species human disease modeling using patient-derived extracellular vesicles.

Reliable disease models are critical for medicine advancement. Here, we established a versatile human disease model system using patient derived extracellular vesicles (EVs), which transfer a pathology-inducing cargo from a patient to a recipient naïve model organism. As a proof of principle, we applied extracellular vesicles from serum of muscular dystrophy patients to C. elegans and demonstrated their capability to induce a spectrum of muscle pathologies including lifespan shortening and robust impairment of muscle organization and function. This demonstrates that patient-derived extracellular vesicles can deliver disease-relevant pathologies between species and can be exploited for establishing novel personalized human disease models. Such models can potentially be employed for disease diagnosis and prognosis, for analyzing treatment responses and drug screening and for the identification of disease-transmitting cargo of patient extracellular vesicles and their cellular targets. This system complements traditional genetic disease models and enables modelling of multifactorial diseases and of those not yet associated with specific genetic mutations.