Abstract
Acute respiratory distress syndrome (ARDS) is a serious and potentially fatal acute inflammatory lung condition which currently has no specific treatments targeting its pathophysiology. However, mesenchymal stem cells have been shown to have very promising therapeutic potential, and recently, it has been established that their effect is largely due to the transfer of extracellular vesicles (EVs). EVs have been shown to transfer a variety of substances such as mRNA, miRNA, and even organelles such as mitochondria in order to ameliorate ARDS in preclinical models. In addition, the fact that they have been proven to have the same effect as their parent cells combined with their numerous advantages over whole cell administration means that they are a promising candidate for clinical application that merits further research.
Highlights
Acute respiratory distress syndrome (ARDS) is a serious and potentially fatal acute inflammatory lung condition which currently has no specific treatments targeting its pathophysiology
Acute respiratory distress syndrome (ARDS) was first described in 1967 but its definition has changed over time[1] with it currently being defined by the Berlin definition, which splits it into three severity levels: mild, moderate, and severe.[2]
We have demonstrated for the first time that transfer of functional mitochondria in extracellular vesicles (EVs) resulted in macrophage polarization from a pro-inflammatory toward an anti-inflammatory phenotype through enhancement in oxidative phosphorylation.[24]
Summary
Acute respiratory distress syndrome (ARDS) was first described in 1967 but its definition has changed over time[1] with it currently being defined by the Berlin definition, which splits it into three severity levels: mild, moderate, and severe.[2]. When used in preclinical models of ARDS, MSCs have been shown to greatly reduce inflammation and while the mechanism behind this is still not known precisely, it is known that MSCs reduce the levels of many pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 while increasing the levels of cytokines which reduce inflammation like IL-4, IL-5, and IL-10.16 In addition, MSCs promote bacterial clearance both directly by secreting antimicrobial peptides and proteins such as LL-3717 and lipocalin[18] as well as indirectly by activating host monocytes, macrophages and neutrophils which phagocytose the bacteria.[19,20,21,22,23,24] Their secretion of substances such as keratinocyte growth factor (KGF) has been shown to be essential in alveolar fluid clearance and restoration of epithelial permeability.[19,25] For further information about the properties of MSCs in ARDS, consider consulting the reviews by Johnson et al[16] and Walter et al.[26] Due to these therapeutic effects, MSCs are being actively developed toward clinical application. MSCs have been shown to be safe in early phase clinical trials such as the START trial phase 1 and 2a.27,28 In addition, a study known as MUST-ARDS conducted by Athersys
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