International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19

Börger, Verena; Weiss, Daniel J.; Anderson, Johnathon D.; Borràs, Francesc E.; Bussolati, Benedetta; Carter, David R. F.; Dominici, Massimo; Falcón‐Pérez, Juan Manuel; Gimona, Mario; Hill, Andrew; Hoffman, Andrew M.; Kleijn, Dominique P.V. de; Levine, Bruce L.; Lim, Rebecca; Lötvall, Jan; Mitsialis, S. Alex; Monguió‐Tortajada, Marta; Muraca, Maurizio; Nieuwland, Rienk; Nowocin, Anna; O’Driscoll, Lorraine; Ortiz, Luis A.; Phinney, Donald G.; Reischl, Ilona; Rohde, Eva; Sanzenbacher, Ralf; Théry, Clotilde; Toh, Wei Seong; Witwer, Kenneth W.; Lim, Sai Kiang; Giebel, Bernd

doi:10.1016/j.jcyt.2020.05.002

Cited by 104 publications

(94 citation statements)

References 45 publications

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“…Before testing these promising EV therapies on human subjects, a number of translational issues should be carefully considered as summarized by Rohde et al [92] and as recently recommended by the ISEV and International Society for Cell & Gene Therapy (ISCT) communities [93]. Firstly, the optimal EV source should be identified.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of extracellular vesicle‐based treatments for lung injury: are EVs a potential therapy for COVID‐19?

Khalaj

Figueira

Antounians

et al. 2020

J of Extracellular Vesicle

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Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors. Most patients with severe COVID-19 infections who died had developed ARDS. Currently, ARDS is treated with supportive measures, but regenerative medicine approaches including extracellular vesicle (EV)-based therapies have shown promise. Herein, we aimed to analyse whether EV-based therapies could be effective in treating severe pulmonary conditions that affect COVID-19 patients and to understand their relevance for an eventual therapeutic application to human patients. Using a defined search strategy, we conducted a systematic review of the literature and found 39 articles (2014-2020) that reported effects of EVs, mainly derived from stem cells, in lung injury models (one large animal study, none in human). EV treatment resulted in: (1) attenuation of inflammation (reduction of pro-inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production). These effects were mediated by the release of EV cargo and identified factors including miRs-126, −30b-3p, −145, −27a-3p, syndecan-1, hepatocyte growth factor and angiopoietin-1. This review indicates that EV-based therapies hold great potential for COVID-19 related lung injuries as they target multiple pathways and enhance tissue regeneration. However, before translating EV therapies into human clinical trials, efforts should be directed at developing good manufacturing practice solutions for EVs and testing optimal dosage and administration route in large animal models.

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Section: Discussionmentioning

confidence: 99%

Systematic review of extracellular vesicle‐based treatments for lung injury: are EVs a potential therapy for COVID‐19?

Khalaj

Figueira

Antounians

et al. 2020

J of Extracellular Vesicle

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show abstract

“…The beneficial effects of EVs have further been observed in an ischemic stroke model (53,54). Since COVID-19 may be associated with damage to other organs in addition to the lungs and has been associated with ischemic stroke, EVs could be a particularly promising therapy in this context (19). However, only one prospective study has evaluated the effects of EVs (specifically, exosomes from bone marrow-derived MSCs) in COVID-19 patients (55).…”

Section: Rationale For Using Extracellular Vesicles In Covid-19mentioning

confidence: 99%

“…Cell-free therapies, such as the MSC secretome (obtained as conditioned medium) and extracellular vesicles (EVs) from MSCs, have been studied in ARDS ( 16 ) and multiple organ dysfunction syndrome (MODS) ( 17 , 18 ) for their anti-inflammatory and anti-fibrogenic effects, as well as their epithelial and endothelial regenerative properties. However, many researchers and international societies, including the International Society for Extracellular Vesicles (ISEV) and the International Society for Cellular and Gene Therapies (ISCT), have expressed concern regarding the use of EVs—whether derived from MSCs or from other cell sources—in the treatment of COVID-19 ( 19 ). Clinical trials are encouraged; however, the use of EVs for any purpose in COVID-19 is not endorsed by ISEV and ISCT until proper regulation of manufacturing, quality control protocols, and clinical trial design are in place, in order to avoid the stem-cell industry trying to sell unregulated MSC treatments ( 19 ).…”

Section: Cell-free Therapies For Covid-19mentioning

confidence: 99%

“…However, many researchers and international societies, including the International Society for Extracellular Vesicles (ISEV) and the International Society for Cellular and Gene Therapies (ISCT), have expressed concern regarding the use of EVs—whether derived from MSCs or from other cell sources—in the treatment of COVID-19 ( 19 ). Clinical trials are encouraged; however, the use of EVs for any purpose in COVID-19 is not endorsed by ISEV and ISCT until proper regulation of manufacturing, quality control protocols, and clinical trial design are in place, in order to avoid the stem-cell industry trying to sell unregulated MSC treatments ( 19 ). In this context, the implementation of computer-controlled bioreactors ( 20 ) and the development of standard operating procedures (SOPs) for obtaining a Good Manufacturing Practice (GMP)-grade MSC secretome and its components are necessary for clinical applications ( 21 ).…”

Section: Cell-free Therapies For Covid-19mentioning

confidence: 99%

“…Administration of EVs has proven safe and effective in preclinical studies of lung injury and sepsis models ( 16 , 18 , 19 , 46 – 48 ). In preclinical studies, EV therapy ameliorated acute lung injury ( 49 , 50 ) and was equally or even more effective than MSCs in mitigating lung inflammation and pathological damage ( 41 , 51 ).…”

Section: Rationale For Using Extracellular Vesicles In Covid-19mentioning

confidence: 99%

See 2 more Smart Citations

Cell-Free Therapies: Novel Approaches for COVID-19

Maron‐Gutierrez

Rocco

2020

Front. Immunol.

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A Review of Extracellular Vesicles in COVID‐19 Diagnosis, Treatment, and Prevention

Xie

et al. 2023

Advanced Science

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The 2019 novel coronavirus disease (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is ongoing, and has necessitated scientific efforts in disease diagnosis, treatment, and prevention. Interestingly, extracellular vesicles (EVs) have been crucial in these developments. EVs are a collection of various nanovesicles which are delimited by a lipid bilayer. They are enriched in proteins, nucleic acids, lipids, and metabolites, and naturally released from different cells. Their natural material transport properties, inherent long‐term recycling ability, excellent biocompatibility, editable targeting, and inheritance of parental cell properties make EVs one of the most promising next‐generation drug delivery nanocarriers and active biologics. During the COVID‐19 pandemic, many efforts have been made to exploit the payload of natural EVs for the treatment of COVID‐19. Furthermore, strategies that use engineered EVs to manufacture vaccines and neutralization traps have produced excellent efficacy in animal experiments and clinical trials. Here, the recent literature on the application of EVs in COVID‐19 diagnosis, treatment, damage repair, and prevention is reviewed. And the therapeutic value, application strategies, safety, and biotoxicity in the production and clinical applications of EV agents for COVID‐19 treatment, as well as inspiration for using EVs to block and eliminate novel viruses are discussed.

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International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19

Cited by 104 publications

References 45 publications

Systematic review of extracellular vesicle‐based treatments for lung injury: are EVs a potential therapy for COVID‐19?

Systematic review of extracellular vesicle‐based treatments for lung injury: are EVs a potential therapy for COVID‐19?

Cell-Free Therapies: Novel Approaches for COVID-19

A Review of Extracellular Vesicles in COVID‐19 Diagnosis, Treatment, and Prevention

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