Stem cells from the amniotic fluid: a promising tool to face the cytokine storm associated to SARS‐CoV‐2 infections

Vaiasicca, Salvatore; Corradetti, Bruna

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 (MSCs) from the amniotic fluid (AF) and their derivatives, through their immunomodulatory, anti‐oxidant, and regenerative functions, could provide such an option. Next Generation Sequencing analysis of MSCs isolated from human 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. AF‐MSCs also contained bioactive molecules involved in respiratory endothelial protection and repair, such as VEGF, IL‐1, TGF‐β1, EGFR, in extracellular matrix re‐organization or associated with cardiac muscle cell function. Analysis of non‐coding RNAs identified the presence of microRNAs that regulate macrophage polarization (towards an anti‐inflammatory phenotype) and attenuate inflammation, as well as regulate the host response to viral infection. Among those, exosomal miRNAs have been also identified. Building upon these observations, further efforts will be made to elucidate the potential therapeutic use of AF‐MSCs 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.