Extracellular Vesicles from Animal Milk: Great Potentialities and Critical Issues

SIMPLE SUMMARY: Milk represents the main source of nutrition for newborn mammals and serves as the conveyor of maternal messages of a sophisticated signaling system to promote postnatal health. It contains bioactive components that are essential for the development of the newborn immune system such as oligosaccharides, lactoferrin, lysozyme, alpha-lactalbumin, and immunoglobulins. Extracellular vesicles (EVs) were recently identified to be pivotal in this mother-to-child exchange. EVs are micro- and nanosized structures enclosed in a phospholipidic double-layer membrane that are produced by all cell types. They are released in the extracellular environment and reach close and distant cells. EVs can induce the modulation of biological processes in receiving cells after their absorption through the release of the molecular cargo contained within vesicles. In this way, EVs can also serve through immunomodulant anti-inflammatory, angiogenetic, and pro-regenerative actions depending on the cell of origin and patho/physiological conditions. EVs can be recovered from all biological fluids including milk. Over the last decade, the number of studies on milk-derived EVs (mEVs) has grown exponentially, first for human milk and then for that of other mammals. This review aimed to present a summary of animal mEV studies by highlighting potentialities, pointing out the issues in studying vesicles from milk, and focusing attention on analytical methodologies. ABSTRACT: Other than representing the main source of nutrition for newborn mammals, milk delivers a sophisticated signaling system from mother to child that promotes postnatal health. The bioactive components transferred through the milk intake are important for the development of the newborn immune system and include oligosaccharides, lactoferrin, lysozyme, α-La, and immunoglobulins. In the last 15 years, a pivotal role in this mother-to-child exchange has been attributed to extracellular vesicles (EVs). EVs are micro- and nanosized structures enclosed in a phospholipidic double-layer membrane that are produced by all cell types and released in the extracellular environment, reaching both close and distant cells. EVs mediate the intercellular cross-talk from the producing to the receiving cell through the transfer of molecules contained within them such as proteins, antigens, lipids, metabolites, RNAs, and DNA fragments. The complex cargo can induce a wide range of functional modulations in the recipient cell (i.e., anti-inflammatory, immunomodulating, angiogenetic, and pro-regenerative modulations) depending on the type of producing cells and the stimuli that these cells receive. EVs can be recovered from every biological fluid, including blood, urine, bronchoalveolar lavage fluid, saliva, bile, and milk, which is one of the most promising scalable vesicle sources. This review aimed to present the state-of-the-art of animal-milk-derived EV (mEV) studies due to the exponential growth of this field. A focus on the beneficial potentialities for human health and the issues of studying vesicles from milk, particularly for the analytical methodologies applied, is reported.