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

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.

Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios

“…13,38 This technique ensures high EV yield and is the most used isolation method to separate EVs for clinical applications in patients. 45 From 10ml of AFSC conditioned medium, we extracted EVs with a typical double membrane morphology (Fig. 1B), a concentration of 7.47x10 10 and small size according to MISEV2023 (mean= 169±92.8nm; mode= 143nm; Fig.…”

“…13,38 This technique ensures high EV yield and is the most used isolation method to separate EVs for clinical applications in patients. 45 From 10ml of AFSC conditioned medium, we extracted EVs with a typical double membrane morphology ( Fig.1B ), a concentration of 7.47x10 10 and small size according to MISEV2023 (mean= 169±92.8nm; mode= 143nm; Fig.1C ) 39 , and expressing canonical EV markers (CD63, TSG101, FLOT1) without evidence of cellular debris (lack of CANX protein expression; Fig.1D ). It remains controversial whether AFSC-EV biological function varies according to vesicle size.…”

“…EV-based therapies are emerging as a potential new treatment strategy for various conditions, as evidenced by several ongoing clinical trials testing EVs in patients with neoplastic diseases, graft versus host disease, Covid-19, Alzheimer’s disease, Meniere’s disease, and osteoarthritis. 45,80–88 Most of these studies were safety and feasibility phase I/II trials and have shown no undesired effects in the recipients. 45…”

“…45,80–88 Most of these studies were safety and feasibility phase I/II trials and have shown no undesired effects in the recipients. 45…”

“…45,[80][81][82][83][84][85][86][87][88] Most of these studies were safety and feasibility phase I/II trials and have shown no undesired effects in the recipients. 45 We acknowledge that our current study has some limitations that need to be addressed before translating this promising EV-based therapy into clinical practice. The findings herein presented were obtained in an ex-vivo model of oligohydramnios.…”