Majority of the studies focusing on MSC-derived exosomes have demonstrated regenerative potential, immune-modulatory functions, anti-inflammatory effects, similar to their parents, i.e. Mesenchymal stem cells. In preclinical set up, MSC-derived exosomes have demonstrated aptitude as an acellular alternative to cell-based therapy, against Acute Respiratory Distress Syndrome (ARDS). These studies have further confirmed that post-exosomal infusion, the associated cytokine storm and pro-inflammatory signalling biomolecules were considerably reduced that were primarily responsible for ARDS pathogenesis. Further analysis confirmed that the exosomes also increased the level of anti-inflammatory signalling mediators that can reduce the severity of the lung injury through increase permeability and functional aspects of alveolar epithelium, as a result of which, the exchange of oxygen-rich air is easily facilitated.
Further deep diving into the same, the ability of exosomes to transfer mitochondria to alveolar cells further increased their survival rate, and thus, facilitated cellular regeneration. These effects have paved the way towards the therapeutic use of this novel acellular alternative Beyond their effects in preclinical model of acute lung disorders, MSC-derived exosomes were also found to be responsible for direct inhibition of viral multiplication With several studies investigating the bio-distribution of this cellular cargo in preclinical setup, it has been quite evident that these exosomes have the potential to alter a variety of different pathways to facilitate active cellular communication. The intrinsic component of the exosomes, miRNAs, are reportedly found to be the key component that is responsible for many physiological processes, like development, epigenetic alterations, immune regulations, etc. By using near IR dyes, several studies have figured out different techniques to track in-vivo bio-distribution of exosomes upon systemic delivery in different animal models.
Several studies have confirmed their reachability to different organs, like in intra-cerebral haemorrhagic rat models, exosomes could reach to the brain upon the intravenous administration. Intravenous administration of exosomes in a mouse model with acute kidney injury shows their accumulation in the kidneys, further confirming exosomes strong paracrine pathways for instant reachability to the site of injury.
Multiple studies have demonstrated that miRNAs secreted by exosomes are very crucial for accelerated lung recovery, particularly in patients suffering from viral infections like influenza, hypoxia-induced pulmonary hypertension, ventricular induced lung injury, etc. Wang et al. observed and studied active regulation of miRNAs during early and late-stage repair of lung damage in the mouse model. This study further indicated that certain miRNAs like miR-290, miR-21, let-7 and miR-200 played a major role in lung regeneration, immune-regulation, and immune-modulation. Alipoor et al. presented strong experimental evidence that stem cell-derived exosomes can deactivate the signalling pathways associated with hypoxia that can also facilitate reduced hypertension and inflammation, specifically evident in the respiratory disorders. Beyond their effects in a preclinical model of acute lung disorders, MSC-derived exosomes are also found to be responsible for direct inhibition of viral multiplication. Studies have confirmed that MSC-derived exosomes secrete miRNA, which acts as a silencing complex and further alters the expression of the cellular receptors through epigenetic changes that help in blocking the entry of many RNA viruses like influenza, hepatitis C and also Coronavirus. In a pig model of influenza, intra-tracheal administration of MSC-derived exosomes, 12hrs post-infection, significantly reduced virus shredding.
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