Cross-species modeling of muscular dystrophy in Caenorhabditis elegans 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 EVs from the serum of patients with muscular dystrophy to Caenorhabditis 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 EVs can deliver disease-relevant pathologies between species and can be exploited for establishing novel and personalized models of human disease. Such models can potentially be used for disease diagnosis, prognosis, analyzing treatment responses, drug screening and identification of the disease-transmitting cargo of patient-derived EVs and their cellular targets. This system complements traditional genetic disease models and enables modeling of multifactorial diseases and of those not yet associated with specific genetic mutations.