Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics

Abstract

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.

Keywords: COVID-19; SARS-CoV-2; acute respiratory distress syndrome; cell therapy; mesenchymal stem cells; pneumonia.

Figure 1

The mechanisms of MSC therapy in ARDS. The therapeutic effects of MSCs in ARDS involve multiple mechanisms via their secretion of soluble paracrine protein factors and extracellular vesicles (EVs). MSCs can exert anti-inflammatory, anti-apoptotic, and anti-microbial effects, protect the pulmonary endothelial and alveolar epithelial cells, enhance alveolar fluid clearance, and inhibit lung fibrosis

Figure 2

The strategies to optimize MSC therapy in ARDS. MSCs can be genetically modified to overexpress beneficial genes or pre-treated with a series of preconditioning strategies, which can promote their therapeutic effects. The improvement of therapeutic effects may depend on an increase in the engraftment and survival of MSCs in the lung, a decrease in the oxidative injury, and enhanced effects of anti-inflammation, anti-apoptosis, and angiogenesis

Figure 3

The potential of MSC-based therapy in COVID-19 patients with severe pneumonia and ARDS by targeting pathophysiological changes. SARS-CoV-2 infections caused severe pneumonia and ARDS, with significant pathophysiological changes, including inflammation, immune system damages (leukopenia and lymphopenia), secondary infections, and distal organ injuries. However, MSCs have the potential to target these pathophysiological events, acting as a alternative strategy for treating COVID-19 patients with ARDS