Exosome-based strategies for Diagnosis and Therapy

Abstract

Exosomes are small extracellular vesicles (30-120 nm) of endosomal origin, which are gaining the attention of the scientific community. Originally considered only a waste disposal system, they are now emerging as another class of signal mediators. Exosomes are secreted by any cell type and retrieved in every body fluid, such as blood, urine, saliva and amniotic liquid. Remarkably, their biochemical content includes not only lipids and proteins, but also nucleic acids, mainly miRNA and mRNA, with a few reports also indicating the presence of genomic and mitochondrial DNA. Their properties have stimulated extensive research to exploit them as a source of biomarkers for the diagnosis and the follow-up of several pathologies. Furthermore, exosomes are relatively robust and stable, so they appear attractive as gene and drug delivery vehicles. They have also revealed immunomodulatory and regenerative properties, which are encouraging their application for therapeutic purposes. Several issues remain to be addressed: exosome isolation is still time consuming and unsatisfactorily reproducible, making it difficult to compare results among laboratories, improve our knowledge of their physiological function and correlate their features with pathological outcomes. Nevertheless, the number of patents trying to address these problems is growing exponentially and many novelties will reach the scientific community in the next few years.

Extracellular Vesicles in Angiogenesis

“…In addition, several recent reports point to a nonuniform distribution of these proteins in all EV subpopulations. 12,30 Importantly, EVs also carry membrane receptors on their surface that are characteristic of the cells that they have been generated from. In addition to their surface molecules, EVs also carry important soluble mediators, such as cytokines, growth factors, and transcription factors.…”

Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes?

“…Conventional methods of exosome isolation are based on a series of centrifugation steps to exclude cells and cell debris and require more than 10 hours of ultracentrifugation; however, these remain the most economical protocols, especially when large numbers of exosomes are required [55, 56]. Several commercial kits and patented approaches have been developed to improve and simplify the exosome isolation process; Urbanelli et al [57] comprehensively reviewed exosome isolation methods to date. In brief, exosomes can be isolated via ultrafiltration plus size exclusion chromatography, precipitation with polymers and immunoaffinity purification using magnetic beads.…”

Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases

“…In addition, issues related to ectopic tissue formation, infusional toxicity caused by cells lodged in the pulmonary microvasculature, and cellular rejection or unwanted engraftment, have been reported. 4 Studies have shown that MSCs can achieve a therapeutic effect in vivo via paracrine action 5, 6 and direct differentiation. Subsequent studies indicated that MSC-secreted extracellular vesicles (EVs), including microvesicles (MVs; 0.1–1 mm in diameter) and exosomes (40–100 nm in diameter), 7, 8 may contribute to the therapeutic potency of MSCs by mediating cell–cell micro-communication and transporting paracrine factors during angiogenesis, tissue regeneration and immune regulation.…”