Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell‐autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane‐associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome‐based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC‐derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC‐derived exosome‐based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC‐exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation.