Intravenous xenogeneic human cardiosphere-derived cell extracellular vesicles (exosomes) improves behavioral function in small-clot embolized rabbits

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Acute ischemic stroke is devastating to patients and their families because of few viable therapeutic options to promote recovery after reperfusion windows close. Recent breakthroughs in biotechnology have resulted in a reproducible patented process for the purification of extracellular vesicles (EVs) from human cardiosphere-derived cells (CDCs). Because CDC-EVs have many features potentially beneficial to treat acute ischemic stroke, CDC-EVs were evaluated in an established small-clot rabbit embolic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model. Biodistribution studies with fluorescent DiD-labeled CDC-EVs showed intense uptake in the ischemic region of the brain. In this report, we show that intravenous (IV) CDC-EVs (0.75 mg/kg) administered 1-hour post-embolization significantly attenuate behavioral deficits following an embolic stroke in rabbits. In CDC-EV-treated rabbits, P50 (3.63 ± 1.27 mg, n = 24) was increased by 245% over vehicle control (1.05 ± 0.15 mg, n = 24); by comparison, rt-PA increased P50 by 91% (2.01 ± 0.24 mg, n = 23). Importantly, the therapy was also without adverse effects on intracerebral hemorrhage or survival rate of embolized rabbits. Thus, as a first step toward widespread use, CDC-EVs, given adjunctively to routine reperfusion therapy, merit further investigation as a therapeutic candidate for stroke

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