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Review
. 2020 Jan;38(1):15-21.
doi: 10.1002/stem.3061. Epub 2019 Oct 1.

Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

Fanny M Elahi  1 , D Gregory Farwell  2 , Jan A Nolta  3 , Johnathon D Anderson  2
Affiliations
Review

Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

Fanny M Elahi et al. Stem Cells. 2020 Jan.

Abstract

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.

Keywords: exosomes; extracellular vesicles; mesenchymal stem cells; mesenchymal stromal cells; microvesicles.

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Conflict of interest statement

D.G.F. declared research funding from NIH RO1 with Intuitive Surgical as a co‐PI. J.D.A. declared leadership position, stock and intellectual property rights ownership in Somos Therapeutics, Inc. The other authors indicated no financial relationships.

Figures

Figure 1
Figure 1
Mesenchymal stem/stromal cells secrete immunomodulatory and regenerative factors, including canonical secretory protein monomers as well as exosomes. The latter of which has been the subject of increasing preclinical investigation in recent years
Figure 2
Figure 2
Mesenchymal stem cell‐derived exosomes are packaged with a diverse profile of macromolecules, including extracellular, membrane‐bound, cytosolic, and nuclear associated factors
Figure 3
Figure 3
The diversity of, A, species, B, tissue source, C, isolation technique, D, culturing methods, E, disease indication, and F, route of administration represented from over 200 preclinical reports on exosomes derived from mesenchymal stem cells. Abbreviations: BM, bone marrow; CORD, umbilical cord; ESC, embryonic stem cell; FBS, fetal bovine serum; HPLC, high pressure liquid chromatography; IM, intramuscular; IP, intraperitoneal; iPSC, induced pluripotent stem cell; IV, intravenous; MSK, musculoskeletal; PL, placenta; precip, precipitation; SC, subcutaneous; TFF, tangential flow filtration; UC, ultracentrifugation; WJ, Wharton's jelly
See this image and copyright information in PMC

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