The Potential Role of Extracellular Vesicles in COVID-19 Treatment: Opportunity and Challenge

Yan, Yan Yan; Zhou, Wen Min; Wang, Yu Qing; Guo, Qiao Ru; Zhao, Fu Xi; Zhu, Zhuang Yan; Xing, Yan; Zhang, Hai Yan; Aljofan, Mohamad; Jarrahi, Alireza Mosavi; Makabel, Bolat; Zhang, Jian Ye

doi:10.3389/fmolb.2021.699929

Cited by 25 publications

(25 citation statements)

References 206 publications

(209 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have demonstrated that the therapeutic mechanisms of MSCs are largely mediated through the release of paracrine factors like MSC-EVs ( 63 ). MSC-EVs may also be amenable to a broader range of delivery methods, such as aerosol inhalation, which may be particularly relevant in the context of COVID-19 ( 64 ). Although we were unable to perform subgroup analysis to compare the efficacy of MSC-EVs to their parent MSCs in this first edition of our living systematic review, we anticipate that an analysis of this nature will be possible in future updates.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem/stromal cell–based therapies for COVID-19: First iteration of a living systematic review and meta-analysis

et al. 2022

View full text Add to dashboard Cite

Background : Mesenchymal stem/stromal cells (MSCs) and their secreted products are a promising therapy for COVID-19 given their immunomodulatory and tissue repair capabilities. Many small studies were launched at the onset of the pandemic and repeated meta-analysis is critical to obtain timely and sufficient statistical power to determine efficacy. Methods and Findings : All English language published studies identified in our systematic search (up to February 3, 2021) examining the use of MSC-derived products to treat patients with COVID-19 were identified. Risk of bias (RoB) was assessed for all studies. Nine studies were identified (189 patients) and four were controlled (93 patients). Three of the controlled studies reported on mortality (primary analysis) and were pooled through random effects meta-analysis. MSCs decreased the risk of death at study endpoint compared to controls (RR: 0.18, 0.04-0.74; p=0.02; I 2 =0%) although follow-up differed. Among secondary outcomes, IL-6 levels were most commonly reported and were decreased compared to controls (SMD: -0.69, -1.15 to -0.22, p=0.004; I 2 =0%) (n=3 studies). Other outcomes were not reported consistently and pooled estimates of effect were not performed. Substantial heterogeneity was observed between studies in terms of study design. Adherence to published ISCT criteria for MSC characterization was low (2 of 9 studies RoB analysis revealed a low to moderate risk of bias in controlled studies and uncontrolled case series were of good (3 studies) or fair (2 studies) quality. Conclusion : Use of MSCs to treat COVID-19 appears promising, however, few studies were identified and potential risk of bias was detected in all studies. More controlled studies that report uniform clinical outcomes and use MSC products that meet standard ISCT criteria should be performed. Future iterations of our systematic search should refine estimates of efficacy and clarify potential adverse effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem/stromal cell–based therapies for COVID-19: First iteration of a living systematic review and meta-analysis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…COVID-19 caused by the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus type 2) mainly affects the lungs but has also severe effects on multiple other organ systems (cardiovascular, gastrointestinal, hematopoietic, renal, and immune system). The disease is associated with a dysregulated cytokine profile, pathological changes of platelet and lymphocyte numbers, as well as endothelial dysfunction and often involves microthrombosis in the lungs, and acute thrombotic events such as stroke or venous thromboembolism with severe cases presenting with sepsis and multiple organ failure finally leading to death ( Fajgenbaum and June, 2020 ; Koupenova and Freedman, 2020 ; Elbadawi et al, 2021 ; Yan et al, 2021 ). EVs of different cellular origin circulate in plasma of COVID-19 patients ( Zaid et al, 2020 ; Campello et al, 2021 ) and can trigger distinct metabolic and transcriptional responses in recipient cells ( Lam et al, 2021 ).…”

Section: Roles Of Evs In Inflammation Cancer and Thrombosismentioning

confidence: 99%

Extracellular Vesicles Linking Inflammation, Cancer and Thrombotic Risks

Beck¹,

Hochreiter²,

Schmid³

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Extracellular vesicles (EVs) being defined as lipid-bilayer encircled particles are released by almost all known mammalian cell types and represent a heterogenous set of cell fragments that are found in the blood circulation and all other known body fluids. The current nomenclature distinguishes mainly three forms: microvesicles, which are formed by budding from the plasma membrane; exosomes, which are released, when endosomes with intraluminal vesicles fuse with the plasma membrane; and apoptotic bodies representing fragments of apoptotic cells. Their importance for a great variety of biological processes became increasingly evident in the last decade when it was discovered that they contribute to intercellular communication by transferring nucleotides and proteins to recipient cells. In this review, we delineate several aspects of their isolation, purification, and analysis; and discuss some pitfalls that have to be considered therein. Further on, we describe various cellular sources of EVs and explain with different examples, how they link cancer and inflammatory conditions with thrombotic processes. In particular, we elaborate on the roles of EVs in cancer-associated thrombosis and COVID-19, representing two important paradigms, where local pathological processes have systemic effects in the whole organism at least in part via EVs. Finally, we also discuss possible developments of the field in the future and how EVs might be used as biomarkers for diagnosis, and as vehicles for therapeutics.

show abstract

“…The COVID-19 pandemic has pushed doors and opened new avenues in certain research areas [ 90 ]. Several trials were registered during the pandemic to explore the untapped potential of EVs in lung pathology associated with SARS-CoV-2 infection [ 91 ]. Clinical trials NCT04491240, NCT04276987, NCT04602442, and NCT04313647 are focused on investigating the safety and efficacy of MSC-derived EVs as an aerosol inhalation to harness the cytokine storm in severe hospitalized patients [ 92 ].…”

Section: Clinical Trials Evaluating Peripherally Targeted Extracellul...mentioning

confidence: 99%

Targeted Drug Delivery to the Central Nervous System Using Extracellular Vesicles

et al. 2022

View full text Add to dashboard Cite

The blood brain barrier (BBB) maintains the homeostasis of the central nervous system (CNS) and protects the brain from toxic substances present in the circulating blood. However, the impermeability of the BBB to drugs is a hurdle for CNS drug development, which hinders the distribution of the most therapeutic molecules into the brain. Therefore, scientists have been striving to develop safe and effective technologies to advance drug penetration into the CNS with higher targeting properties and lower off-targeting side effects. This review will discuss the limitation of artificial nanomedicine in CNS drug delivery and the use of natural extracellular vesicles (EVs), as therapeutic vehicles to achieve targeted delivery to the CNS. Information on clinical trials regarding CNS targeted drug delivery using EVs is very limited. Thus, this review will also briefly highlight the recent clinical studies on targeted drug delivery in the peripheral nervous system to shed light on potential strategies for CNS drug delivery. Different technologies engaged in pre- and post-isolation have been implemented to further utilize and optimize the natural property of EVs. EVs from various sources have also been applied in the engineering of EVs for CNS targeted drug delivery in vitro and in vivo. Here, the future feasibility of those studies in clinic will be discussed.

show abstract

The Potential Role of Extracellular Vesicles in COVID-19 Treatment: Opportunity and Challenge

Cited by 25 publications

References 206 publications

Mesenchymal stem/stromal cell–based therapies for COVID-19: First iteration of a living systematic review and meta-analysis

Mesenchymal stem/stromal cell–based therapies for COVID-19: First iteration of a living systematic review and meta-analysis

Extracellular Vesicles Linking Inflammation, Cancer and Thrombotic Risks

Targeted Drug Delivery to the Central Nervous System Using Extracellular Vesicles

Contact Info

Product

Resources

About