Abstract

A Human Kidney and Liver Organoid-based Organ-on-a-chip Model to Study the Therapeutic Effects and Biodistribution of Mesenchymal Stromal Cell-derived Extracellular Vesicles

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. Biodistribution 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. We developed an organoid-based organ-on-a-chip model to assess the efficacy and biodistribution of these sEVs. The human background allows for in-depth analysis of the MoA and identification of potential side effects and accelerated development of EV-based therapeutics.