Therapeutic potential of exosomes from mesenchymal stromal cells in sepsis
Authors: Matvieienko M.S. , Hladkykh F.V. , Оleksiuk О.B. 
Published: December 2024

Background. The World Health Organization has recognized sepsis as one of the global health priorities. Sepsis is defined as the development of life-threatening multiple organ dysfunction caused by an unregulated immune response of the body (systemic inflammatory response syndrome) to infection, which is the direct cause of death of critically ill patients in the intensive care unit. Despite advances in infusion resuscitation, antibiotic use, and organ support that have combined to reduce in-hospital mortality, patients with sepsis exhibit increased long-term morbidity and mortality. Many sepsis survivors suffer long-term physical and cognitive impairments and have a higher mortality rate than the general population. To date, several preclinical studies have identified mesenchymal stromal cells (MSCs) as a novel tool for sepsis therapy due to their ability to suppress the inflammatory response.

Purpose – to give an assessment of the prospective study of the therapeutic effectiveness of MSC derivatives in sepsis.

Materials and Methods. Publications were selected based on the databases PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and Google Scholar, which covered information on the therapeutic effects of exosomes obtained from MSCs in sepsis. At the first stage, literature sources were searched using key words: sepsis, extracellular vesicles, exosomes, mesenchymal stromal cells, acute respiratory distress syndrome, acute kidney injury, myocardial dysfunction, liver damage. At the second stage, summaries of articles were studied and publications that did not meet the research criteria were excluded. At the third stage, the full texts of the selected articles were studied for compliance with the criteria for inclusion in the literature list and research relevance.

Results. Taking into account the key pathogenetic links of sepsis, the data on the therapeutic effectiveness of exosomes from MSCs in four leading sepsis syndromes – acute lung injury, kidney damage, cardiovascular disorders, and liver damage caused by sepsis – are described. Acute lung injury is the most common organ injury in patients with sepsis, increasing mortality to 40%. Exosomes are key effectors of pulmonary endothelial interactions with neighboring and circulating cells and mediators for modulating local immune thrombosis, inflammatory cell adhesion, and alveolar unit integrity. A number of experimental studies have demonstrated the effectiveness of using exosomes from MSCs in simulated acute lung injury in animals. Acute kidney injury (AKI) occurs in 20% of patients with sepsis, and cardiac involvement is a common disorder in patients with sepsis, and approximately 50% of patients with sepsis show signs of myocardial dysfunction. Inflammation and coagulation are critical components in sepsis, involving leukocytes, platelets, and vascular endothelial cells. Hepatoprotective activity of exosomes from MSCs has been demonstrated in a number of acute liver injuries, in particular those induced by tetrachloromethane, concanavalin A, and ischemia-reperfusion liver injury models.

Conclusions. A number of studies have demonstrated that MSC-derived secretome exhibits therapeutic effects similar to those seen after MSC transplantation. Exosomes derived from both immune and non-immune cells play an important role in immune regulation, which can contribute to the pathology of many diseases by mediating immune stimulation or suppression. Exosomes obtained from MSCs have protective activity in the leading syndromes of sepsis – in acute lung injury, in kidney damage, in cardiovascular disorders and against the background of liver damage caused by sepsis.