Salvatore Vaiasicca1 and Bruna Corradetti2,3
1Department of Science and Environmental Life, Università Politecnica delle Marche, via Brecce Bianche, 60122, Ancona, Italy;
2 Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave., Houston, TX 77030, USA;
3 Center of NanoHealth, Swansea University Medical School, Singleton Park, Swansea, UK
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 19 (COVID-19) is associated with significant morbidity and mortality. Despite significant progress since the emergence of this disease, efficacious therapeutics are still urgently required. Infection is associated with a broad spectrum of symptoms and varying disease severity. In severe cases, a multi-organ disease is apparent, involving the respiratory, coagulation, immune and cardiac systems. A central tenant of severe disease is an excessive immune response to infection leading to a cytokine storm and associated organ and tissue damage. Immunological therapies capable of attenuating the cytokine storm may therefore provide novel treatment options, and the present study explored whether mesenchymal stem cells (MSC) and their derivatives, through their immunomodulatory, anti-oxidant, and regenerative functions, could provide such an option.
Next Generation Sequencing analysis of MSC isolated from chorionic villi (CV) and amniotic fluid (AF) identified a plethora of molecules with the potential to positively influence the prognosis in SARS-Cov-2 infection patients. These included mRNAs involved in the regulation of several immune pathways that are basis of the impaired immune response and cytokine storm caused seen in SARS-CoV-2-positive patients, such as: HIF-1, IL-17, Toll-like receptors, RAP1, TNF, WNT, PI3K-Akt and NF-kappa B signalling. CV and AF-MSC also contained bioactive molecules involved in respiratory endothelial protection and repair, such as VEGF, IL-1, TGF-β1, EGFR, molecules involved in extracellular matrix re-organization and those associated with cardiac muscle cell function. Analysis of non-coding RNAs identified the presence of microRNAs (ie. miR-27a, miR-181 and miR-145) that regulate macrophage polarization (towards an anti-inflammatory phenotype) and attenuate inflammation, as well as regulate the host response to viral infection. They are also present in extracellular vesicles, primarily exosomes, released by cells.
Building upon these observations, further efforts will be made to elucidate the potential therapeutic use of CV- and AF-MSC and their derivatives in combating the immune-related side effects of SARS-CoV-2. The successful incorporation of such an MSC-based therapy into the treatment regimen of SARS-CoV-2 infected patients has significant potential to reduce the morbidity and mortality associated with COVID-19.