Abstract

Investigating Extracellular Vesicle-based Therapeutic Options Using Alternatives For Animal Models

Bas van Balkom, Assistant Professor, University Medical Center Utrecht

Mesenchymal stromal cell (MSC)-derived small EVs (sEVs) show therapeutic potential in multiple disease models, including kidney injury. Clinical translation of sEVs requires further preclinical and regulatory developments, like elucidation of the mode of action (MoA) and formulation of safety and release criteria. sEVs tend to accumulate in the liver and at sites of injury. Bio-distribution knowledge is crucial to assess MoA, efficacy and safety, and can be obtained using labelled sEVs in animal models, which come with ethical concerns, are time-consuming and expensive, and do not represent all human physiological processes equally well. Our models recapitulate the efficacy and bio-distribution of MSC-sEVs as observed in animal models and provide alternatives for animal experiments. Their systemic or human background allows for in-depth analysis of the MoA and identification of potential side effects and accelerated development of EV-based therapeutics.