The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV‐associated functional activities. Finally, a checklist is provided with summaries of key points.

Cellular senescence acts as a barrier to cancer progression, and microRNAs (miRNAs) are thought to be potential senescence regulators. However, whether senescence-associated miRNAs (SA-miRNAs) contribute to tumor suppression remains unknown. Here, we report that miR-22, a novel SA-miRNA, has an impact on tumorigenesis. miR-22 is up-regulated in human senescent fibroblasts and epithelial cells but down-regulated in various cancer cell lines. miR-22 overexpression induces growth suppression and acquisition of a senescent phenotype in human normal and cancer cells. miR-22 knockdown in presenescent fibroblasts decreased cell size, and cells became more compact. miR-22–induced senescence also decreases cell motility and inhibits cell invasion in vitro. Synthetic miR-22 delivery suppresses tumor growth and metastasis in vivo by inducing cellular senescence in a mouse model of breast carcinoma. We confirmed that CDK6, SIRT1, and Sp1, genes involved in the senescence program, are direct targets of miR-22. Our study provides the first evidence that miR-22 restores the cellular senescence program in cancer cells and acts as a tumor suppressor.

A substantial proportion of patients with acute graft‐versus‐host disease (aGVHD) respond to cell therapy with culture‐expanded human bone marrow mesenchymal stromal/stem cells (BM‐MSCs). However, the mechanisms by which these cells can ameliorate aGVHD‐associated complications remain to be clarified. We show here that BM‐MSC‐derived extracellular vesicles (EVs) recapitulated the therapeutic effects of BM‐MSCs against aGVHD. Systemic infusion of human BM‐MSC‐derived EVs prolonged the survival of mice with aGVHD and reduced the pathologic damage in multiple GVHD‐targeted organs. In EV‐treated GVHD mice, CD4+ and CD8+ T cells were suppressed. Importantly, the ratio of CD62L‐CD44+ to CD62L + CD44‐ T cells was decreased, suggesting that BM‐MSC‐derived EVs suppressed the functional differentiation of T cells from a naive to an effector phenotype. BM‐MSC‐derived EVs also preserved CD4 + CD25 + Foxp3+ regulatory T cell populations. In a culture of CD3/CD28‐stimulated human peripheral blood mononuclear cells with BM‐MSC‐derived EVs, CD3+ T cell activation was suppressed. However, these cells were not suppressed in cultures with EVs derived from normal human dermal fibroblasts (NHDFs). NHDF‐derived EVs did not ameliorate the clinical or pathological characteristics of aGVHD in mice, suggesting an immunoregulatory function unique to BM‐MSC‐derived EVs. Microarray analysis of microRNAs in BM‐MSC‐derived EVs versus NHDF‐derived EVs showed upregulation of miR‐125a‐3p and downregulation of cell proliferative processes, as identified by Gene Ontology enrichment analysis. Collectively, our findings provide the first evidence that amelioration of aGVHD by therapeutic infusion of BM‐MSC‐derived EVs is associated with the preservation of circulating naive T cells, possibly due to the unique microRNA profiles of BM‐MSC‐derived EVs. Stem Cells 2018;36:434–445