Current Perspective on Human Milk Derived Vesicles and Their Potential Therapeutic Use: A Scoping Review.

Human milk-derived extracellular vesicles (HMEVs) recently gained significant attention due to their role in mother-child communication and biomedical application potential. We here provide a systematic scoping review together with interactive figures and comprehensive overview tables summarising the current published knowledge base on HMEVs with a particular perspective on therapeutically relevant aspects, including consensus and divergence of isolation, characterisation, and investigation in preclinical models. Extraction from Embase and MEDLINE and systematic stratification yielded 113 original articles for further analysis. Key themes and emerging issues that became evident included (1) need for more systematic investigation and documentation of basic but essential aspects such as storage, processing parameters and endotoxin levels. (2) Changes of EV concentrations, composition, and potentially also biological activities with gestational age at birth, lactation stage and maternal background need to be taken into consideration to (3) define relevant donor selection criteria. For clinical translation, (4) the definition of mechanisms of action and relevant safety parameters is still lacking while imperative to define critical quality attributes. Eventually, (5) the availability of validated disease models to evaluate therapeutic potency represents a particular challenge for HMEVs since therapeutic approaches inherently focus on infant physiology which is difficult to model in rodents.