Mesenchymal stromal cell secretome in liver failure: Perspectives on COVID-19 infection treatment

Abstract

Due to their immunomodulatory potential and release of trophic factors that promote healing, mesenchymal stromal cells (MSCs) are considered important players in tissue homeostasis and regeneration. MSCs have been widely used in clinical trials to treat multiple conditions associated with inflammation and tissue damage. Recent evidence suggests that most of the MSC therapeutic effects are derived from their secretome, including the extracellular vesicles, representing a promising approach in regenerative medicine application to treat organ failure as a result of inflammation/fibrosis. The recent outbreak of respiratory syndrome coronavirus, caused by the newly identified agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has forced scientists worldwide to use all available instruments to fight the infection, including the inflammatory cascade caused by this pandemic disease. The use of MSCs is a valid approach to combat organ inflammation in different compartments. In addition to the lungs, which are considered the main inflammatory target for this virus, other organs are compromised by the infection. In particular, the liver is involved in the inflammatory response to SARS-CoV-2 infection, which causes organ failure, leading to death in coronavirus disease 2019 (COVID-19) patients. We herein summarize the current implications derived from the use of MSCs and their soluble derivatives in COVID-19 treatment, and emphasize the potential of MSC-based therapy in this clinical setting.

Keywords: COVID-19; Inflammation; Mesenchymal stromal cell; Organ failure; SARS-CoV-2; Transplantation.

Figure 1

Schematic representation of severe acute respiratory syndrome coronavirus 2 impact on lungs and liver. Cytokine storm with the cascade triggered by natural killer (NK) cells, T helper (Th) cell and monocytes, and the production of inflammatory cytokines (interleukin 1 beta [IL-1b], Il-2, IL-6, IL-8, IL-10, Il-17, interferons [IFNs], IFN-induced protein 10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor [GM-CSF]). The infection in the liver causes an increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and bilirubin, and a decrease in albumin. Mesenchymal stromal cells (MSCs) can reduce the inflammatory response by extracellular vesicle (EV) release (large ≥ 200 nm and small ≤ 150 nm). ER: Endoplasmic reticulum; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.