Stem Cells. 2019 Aug 5. doi: 10.1002/stem.3061. [Epub ahead of print]

Concise Review: Preclinical Translation of Exosomes Derived from Mesenchymal Stem/Stromal Cells.

Elahi FM¹, Farwell DG², Nolta JA³, Anderson JD².

Abstract

Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizonal transfer of various macromolecules previously believed to be cell-autonomous in nature including non-secretory 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 are over 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 is promising, several outstanding questions remain to be answered that warrant further preclinical investigation. SIGNIFICANCE STATEMENT: Mesenchymal stem/stromal cells (MSCs) are under clinical development for the treatment of numerous disease indications. There is growing interest surrounding the therapeutic application of purified and concentrated regenerative factors secreted by MSCs, particularly exosome-enriched fractions (MEX) which are now understood to be key active pharmaceutical ingredients of MSC-based therapies. This review summarizes the current state of preclinical development of MEX parsed from over 200 peer reviewed reports utilizing various animal models. It also discusses opportunities that may be addressed which would help strategically advance the field of MEX-based therapeutic development.