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

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 stromal 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. © 2021 The authors.

Secretome of Multipotent Mesenchymal Stromal Cells as a Promising Treatment and for Rehabilitation of Patients with the Novel Coronaviral Infection.

As a rule, coronavirus infections are mild in healthy adults and do not require special approaches to treatment. However, highly pathogenic strains, particularly the recently isolated SARS-CoV2, which causes COVID-19 infection, in about 15% of cases lead to severe complications, including acute respiratory distress syndrome, which causes high patient mortality. In addition, a common complication of COVID-19 is the development of pulmonary fibrosis. Why is the novel coronavirus so pathogenic? What new treatments can be proposed to speed up the recovery and subsequent rehabilitation of the organism? In 2020, over 34 000 scientific articles were published on the structure, distribution, pathogenesis, and possible approaches to the treatment of infection caused by the novel SARS-CoV2 coronavirus. However, there are still no definitive answers to these questions, while the number of the diseased is increasing daily. One of the comprehensive approaches to the treatment of the consequences of the infection is the use of multipotent human mesenchymal stromal cells and products of their secretion (secretome). Acting at several stages of the development of the infection, the components of the secretome can suppress the interaction of the virus with endothelial cells, regulate inflammation, and stimulate lung tissue regeneration, preventing the development of fibrosis. The results of basic and clinical research on this topic are summarized, including our own experimental data, indicating that cell therapy approaches can be successfully applied to treat patients with COVID-19.