Liver injury associated with acute respiratory distress syndrome and the prospects of mesenchymal stem cells therapy for liver failure

Abstract

The pathogenesis of acute respiratory distress syndrome (ARDS) includes neutrophilic alveolitis, alteration of alveolar epithelium and endothelium, formation of hyaline membranes and microvascular thrombosis, which results in an acute hypoxemic respiratory failure. ARDS results in major structural and cellular changes in organs and organ systems. It causes liver dysfunction in critical patients through paracrine action of cytokines and other pro-inflammatory mediators as well as hypoxemia, oxidative stress, toxins and hypoperfusion. Coronavirus disease 2019 (COVID-19)-associated ARDS affects liver through the development of systemic inflammatory response syndrome and hypoxia as well as cytokine storm. Liver injury manifests itself as increased plasma levels of hepatic transaminases and cholestatic liver enzymes. Stem cell therapy is one of the promising modern methods for treating ARDS-induced liver failure. Many studies showed the ability of multipotent mesenchymal stem cells (MMSCs) to differentiate into functional hepatocyte-like cells, which were then successfully used for liver regeneration. MMSCs were proven to be able to prevent the apoptosis of hepatocytes, as well as have anti-fibrotic and anti-inflammatory activity which allows their successful use in the treatment of ARDS-induced liver injury.