PMC:7264098 / 23180-25845 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7264098","sourcedb":"PMC","sourceid":"7264098","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7264098","text":"In the majority of clinical trials investigating the treatment of SARS-CoV-2 infections so far, MSCs are delivered via the intravenous route. Since intravenous route does not specifically target lungs, the inhalation route that delivers cells directly to lungs could be more effective. However, uniform delivery of cells to lungs through inhalation is technically challenging (Kim et al., 2016; Kim and Chrzanowski, 2019). Strong evidence is emerging to suggest that the therapeutic potential of MSCs is attributed mostly to their secreted EVs via paracrine effects, and MSCs could also be referred to as medicinal signaling cells (Bjørge et al., 2018; Kim et al., 2019). Delivery of EVs to lungs is feasible and exogenous EVs can facilitate prompt activity directly at the injured site. There is a pilot clinical study that intends to deliver MSC-derived exosomes via the inhalation route to patients with severe pneumonia arising from SARS-CoV-2 infection (NCT04276987). In this clinical trial, the main advantage of administering MSC-derived exosomes via inhalation route compared to the intravenous administration is the prevention of their aggregation within the injured microcirculation. In addition, MSC-derived exosomes have other advantages over MSCs including lower or no risk of mutagenicity and oncogenicity as well as the storage stability of several weeks or months facilitating less urgent transportation and administration. A recent study using animal models of pulmonary fibrosis also demonstrated therapeutic potential of inhaled lung spheroid cell-secretome and exosomes for lung regeneration (Dinh et al., 2020). While the intravenous route is the most widely used often for the ease of administration albeit invasive, the route of cell delivery should be tailored according to the disease in question and patient's circumstances (Kim and Chrzanowski, 2019). As evident from a number of clinically available inhaled medications for chronic lung disease, the inhalation route of delivering therapeutics to the lungs is a more direct route with lower incidence of adverse effects, compared to the intravenous route. Nevertheless, the environment in the hospital has to be appropriately managed for inhaled administration of a treatment in COVID-19 patients. A number of studies have demonstrated the feasibility of delivering stem cells via spray for direct pulmonary delivery with high viability (Kardia et al., 2016; Kim et al., 2016; Skolasinski et al., 2020). Inhalation route of stem cell administration is an opportunity for efficient delivery of stem cells directly to the lungs, yet it remains an under-explored research area in the 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