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. 2024 May;13(5):e12433.
doi: 10.1002/jev2.12433.

Extracellular vesicles as human therapeutics: A scoping review of the literature

Clorinda Fusco  1 , Giusy De Rosa  1 , Ilaria Spatocco  1 , Elisabetta Vitiello  1 , Claudio Procaccini  2   3 , Chiara Frigè  4 , Valeria Pellegrini  4 , Rosalba La Grotta  4 , Roberto Furlan  5 , Giuseppe Matarese  1   2 , Francesco Prattichizzo  4 , Paola de Candia  1
Affiliations

Extracellular vesicles as human therapeutics: A scoping review of the literature

Clorinda Fusco et al. J Extracell Vesicles. 2024 May.

Abstract

Extracellular vesicles (EVs) are released by all cells and contribute to cell-to-cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested. In this scoping review, we searched PubMed and other databases up to 31 December 2023 and, starting from 13,567 records, we selected 40 pertinent published studies testing EVs as therapeutics in humans. The analysis of those 40 studies shows that they are all small pilot trials with a large heterogeneity in terms of administration route and target disease. Moreover, the absence of a placebo control in most of the studies, the predominant local application of EV formulations and the inconsistent administration dose metric still impede comparison across studies and firm conclusions about EV safety and efficacy. On the other hand, the recording of some promising outcomes strongly calls out for well-designed larger studies to test EVs as an alternative approach to treat human diseases with no or few therapeutic options.

Keywords: clinical trials; exosomes; extracellular vesicles; therapeutics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Work flow for the scoping review. The three phases of the work (identification, screening and analysis) are differentiated by background colours. In the analysis box, the different studies are subdivided by disease type, a classification also followed in the Results section.
FIGURE 2
FIGURE 2
Geography of EV‐based clinical studies. World map highlighting the geographic locations (colour code refers to macro‐areas, as indicated) where the identified 40 studies were coordinated (based on the last author's affiliation). Several of the studies were multicentric, which is not reported in the figure.
FIGURE 3
FIGURE 3
Main characteristics of the EV‐based clinical studies. Pie charts showing the distribution, among the 40 selected publications, of clinical study type (a); the mode of comparison (b) and the disease treated (c). GvHD, graft versus host disease; TBC, temporal bone cavity.
FIGURE 4
FIGURE 4
EV cell source, isolation, characterization and administration in the EV‐based clinical studies. (a,b) Pie charts showing the relative quantities of studies making use of specific biological sources for the EV preparations (a) and the relative origin of mesenchymal stem cells for the specific studies using those cells as EV source (b). (c) Pie chart showing the relative quantities of studies making use of specific isolation procedures for the EV preparations. (d) Contingency stacked bar graph showing the relative quantities of studies making use of specific characterization methods for the EV preparations. (e,f) Pie charts showing the relative quantities of studies making use of specific administration routes for EVs in the clinics (e) and the relative subtype of local administration (f). BA, Bradford colorimetric assay; BCA, Bicinchoninic acid protein assay; DC protein assay, Detergent compatible protein assay; DLS, Dynamic light scattering; ELISA, Enzyme Linked ImmunoSorbent Assay; EM, Electron microscopy; FACS, Flow cytometry; FTIR, Fourier‐transform infrared spectroscopy; MS, mass spectrometry; NTA, Nanoparticle tracking analysis; TEM, Transmission Electron microscopy; WB, Western blotting.
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