Medical progress: Stem cells as a new therapeutic strategy for COVID-19

Abstract

Currently, the world is facing the SARS-CoV-2 pandemic, coronavirus of acute respiratory distress syndrome 2, causes of COVID-19. Coronaviruses are RNA single-stranded viruses that have an envelope. In addition, coronaviruses are classified into four subfamilies: alpha, beta, gamma and delta coronaviruses. The first of them, cause mildly symptomatic or asymptomatic infections, while beta-coronaviruses are responsible for severe diseases. SARS-CoV-2 belongs to the group of beta-coronaviruses. Current available therapies use corticosteroids to reduce inflammation, non-specific antiviral drugs or antibiotics in the treatment of secondary bacterial infections. In addition, therapies based on the use of hydroxychloroquine, chloroquine, remdesvir, ribavirin, interferon or lopinavir-ritonavir were also initially used. Mesenchemical stem cells (MSCs) are widely used in cell therapies, which include both basic research and clinical trials. Their exceptional effectiveness and safety have been confirmed and documented in many clinical studies, which include a number of inflammatory diseases involving the immune system – one of them is systemic lupus erythematosus. Available data indicate the ability to differentiate MSCs and their immunomodulatory effects. In addition, through interactions with immune cells, which include, but are not limited to, macrophages and dendritic cells, or paracrine secretion, MSCs are able to secrete a number of types of cytokines. MSCs are also characterized by tissue regeneration and regulation of inflammation. Due to their properties, researchers turned to determine whether MSC transplantation is able to improve the outcome of patients with COVID-19 viral pneumonia. The presented review provides not only new knowledge in the field of molecular mechanisms of pro-regenerative action of stem cells, but also have the potential to open up new prospects of action to improve lung tissue regeneration in COVID-19 patients. In addition, in review mentioned about clinical trials using MSCs with a complete status, as well as the latest discoveries in molecular biology, a platform model of pluripotent stem cells in the SARS-CoV-2 study on 3D animal models and nanoconjugates based on stem cells.

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

“…As suggested by successful MSC use in a number of pathological scenarios involving uncontrolled immune activation with consequent tissue damage, like for example H9N2 induced acute lung injury, ARDS, autoimmune diseases and graft-versus-host disease ( Waterman et al, 2010 ; Elgaz et al, 2019 ; Coelho et al, 2020 ; Yen et al, 2020 ; Barros et al, 2021 ; Musial and Gorska-Ponikowska, 2021 ; Su et al, 2021 ), the undeniable immunomodulatory and inflammation relieving properties of MSCs make them putative candidates as rejuvenating factors for the older immune system, on the basis of the documented ability to reduce pro-inflammatory mediators and to promote the expansion of regulatory lymphocyte subsets ( Yeo et al, 2021 ). Also, MSC transplantation can contribute to the amelioration of aging frailty ( Schulman et al, 2018 ; Florea et al, 2019 ; Sun et al, 2019 ), but MSC may exhibit age related deteriorating functions linked to inflammageing, especially in terms of alterations in number and characteristics of extracellular vesicles, DAMP production, excessive IL-6 release, loss of MSC ability to shift monocyte polarization toward M2, and triggering of ineffective hemopoiesis ( Tsuruhara et al, 2017 ; Lee and Yu, 2020 ).…”

Investigating the Immunomodulatory Potential of Dental Pulp Stem Cell Cultured on Decellularized Bladder Hydrogel towards Macrophage Response In Vitro

“…During a cytokine storm, pro-inflammatory cytokines are secreted by the immune system, which triggers an outburst of white blood cells. As a result, suppressing the cytokine storm from eliciting acute respiratory distress syndrome (ARDS) may be one of the most important factors in COVID-19 treatment [ 31 ]. According to the literature, ECM degradation products consistently downregulate pro-inflammatory and upregulate anti-inflammatory genes and proteins, although the exact mechanisms for this ability have not been fully elucidated [ 32 , 33 ].…”

Mesenchymal Stem Cells Can Both Enhance and Inhibit the Cellular Response to DNA Immunization by Genes of Nonstructural Proteins of the Hepatitis C Virus

“…We also showed that the expression of HCV proteins during transfection of mouse cells with plasmid was accompanied by an increase in the level of proinflammatory cytokines, as well as an increase in IFN-γ in the sera of immunized mice in the case of injection of DNA alone or DNA before MSCs. The immunosuppressive effect of MSCs in this case can be compared with that observed when using MSCs for the treatment of patients with COVID-19 [ 26 ]. During the inflammatory response, many proinflammatory cytokines are secreted, including TNFα, IL-1β, IL-2, IL-6, IL-7, IL-12, IL-18, IL-33, IFN-α, and IFN-γ.…”