Cardiac risk assessment of mesenchymal stem cell-derived extracellular vesicles by telemetry in cynomolgus monkeys

Background & Aim Extracellular vesicles (EVs) are small, membrane-bound particles released by cells, playing a pivotal role in intercellular communication. These vesicles carry a diverse range of bioactive molecules, including proteins, lipids, and nucleic acids, which are critical in mediating various physiological and pathological processes. These properties have led to their use as therapeutic agents in a variety of fields. However, because EVs are administered in concentrations and their various components can be distributed throughout the body upon degradation, they may have undesirable pharmacodynamic properties that may be relevant to patient safety. Methods, Results & Conclusion In this study, we performed a telemetry study in cynomolgus monkeys to determine the cardiovascular risk of mesenchymal stem cell (MSC)-derived EVs. Heart rate, blood pressure and electrocardiogram (ECG) were measured using a telemetry system before dosing (0 h) and at 1, 3, 6, 24 and 48 h after a single intravenous administration of extracellular vesicles at a dose of 2×1010 particles/head in a transmitter-loaded cynomolgus monkey. No statistically significant changes in heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure were observed in MSC-derived EVs compared to vehicle controls at any time point. Electrocardiogram measurements showed no significant differences in PR, QRS, RR, QT and QTcF intervals compared to the vehicle control at any time point, and no abnormalities in electrocardiogram waveforms were observed in the animals. In conclusion, MSC-derived EVs did not appear to have an effect on cardiovascular function in cynomolgus monkeys.