Extracellular Vesicles: A New Frontier for Research in Acute Respiratory Distress Syndrome

Abstract

Recent research on extracellular vesicles (EVs) has provided new insights into pathogenesis and potential therapeutic options for acute respiratory distress syndrome (ARDS). EVs are membrane-bound anuclear structures that carry important intercellular communication mechanisms, allowing targeted transfer of diverse biologic cargo, including protein, mRNA, and microRNA, among several different cell types. In this review, we discuss the important role EVs play in both inducing and attenuating inflammatory lung injury in ARDS as well as in sepsis, the most important clinical cause of ARDS. We discuss the translational challenges that need to be overcome before EVs can also be used as prognostic biomarkers in patients with ARDS and sepsis. We also consider how EVs may provide a platform for novel therapeutics in ARDS.

Cell-Free Therapies: Novel Approaches for COVID-19

“…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 antiinflammatory and anti-fibrogenic effects, as well as their epithelial and endothelial regenerative properties. However, FIGURE 1 | Potential effects of pharmaceutical preparations of MSC secretome on different organs involved in COVID-19.…”

“…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 ).…”

“…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 ).…”

Liver-lung axes in alcohol-related liver disease

“…28 Indeed, it is now hypothesized that EVs contribute to the development and severity of ARDS. 29 Furthermore, remote preconditioning, such as the cardioprotective effect of hindlimb ischemia-reperfusion injury, is also hypothesized to be mediated by EVs (e.g., 30,31 ). The potential role of circulating EVs in mediating liver-lung communication in the context of ALD are not currently understood and would be an interesting target for further investigation.…”

Extracellular vesicles from mesenchymal stem cells as a Covid-19 treatment

“…Extracellular vesicles (EVs) encompass exosomes and ectosomes [4] and can be described as mini-maps of their cells of origin. There is increasing evidence that many, if not all, of the beneficial effects of MSCs can be attributed to their paracrine action via the release of EVs, rather than cellular engraftment and response at the site of injury [5,6]. This suggests that MSC-EVs can produce any of the therapeutic benefits of MSCs.…”