Extracellular Vesicles from Animal Milk: Great Potentialities and Critical Issues.

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.