Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome

Abstract

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a “cytokine storm”, as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a “living anti-inflammatory”, which can “rebalance” the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

“…Patients with IPF have a greater risk of the severe COVID-19 upon infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which itself can induce post-inflammatory pulmonary fibrosis [ 158 , 159 ]. Advanced COVID-19 is characterized by a massive, unrestrained immune activation (the so-called “cytokine storm”) and important deficiencies in immune regulatory mechanisms such as T regulatory cells [ 160 ]. Therefore, an option to combat the disease is to activate anti-inflammatory cells, such as regulatory Treg cells, macrophages and neutrophils, to modulate the immune response via the secretion of cytokines.…”

Mesenchymal stem cells in the treatment of severe COVID-19

“…MSCs are used in the treatment of a range of immune-mediated inflammatory diseases such as lupus erythematous and graft versus host disease [ 2 , 3 ]. Moreover, MSCs reduced mortality in H5N1 influenza and resulted in improved survival in those with H7N9 influenza strain who developed ARDS [ 1 ].…”

Role of biomaterials in the diagnosis, prevention, treatment, and study of corona virus disease 2019 (COVID-19)

“…MSCs can help to regenerate damaged tissues and prevent cytokine storm [ 19 ]. MSCs are ACE2-negative at the gene level and due to their immunomodulatory effect [ 38 – 40 ], anti-inflammatory properties [ 41 , 42 ], and regenerative capacity [ 43 , 44 ] can inhibit the release of unwanted cytokines [ 45 ]. Moreover, MSCs can reduce inflammation and acute lung injury induced by viral infections [ 46 ].…”