SARS-CoV-2 exposed Mesenchymal Stromal Cell from Congenital pulmonary airway malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes

Inflammatory response plays a central role in the complications of congenitalpulmonary airway malformations (CPAM) and severe COVID-19. The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in paediatric MSCs derived from paediatric lung and CPAM tissues, in order to elucidate potential pathways involved in SARS- CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express ACE2 and TRMPSS2. SARS-CoV-2 appears to be unable to infect MSCs-CPAM, when it may be able to enter the MSCs-lung using Toll-like receptor signalling pathway. MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8 and CXCL10) to the presence of SARS-CoV-2, likely as a result of NF-kB cytokine transcription; this route appears silent in MSCs-CPAM and cytokine genes expression is reduced. Using the Notch3 non-canonical pathway, MSCs-lung suppress NF-kB inflammatory transcription and decreased value of p21 suggesting no cell cycle block. In MSCs-CPAM there are not clear signs of active Notch pathway. In conclusion, MSCs-lung appear to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keep stable or reduce the immunomodulatory receptor but they reduce also their cytokines expression. These data are preliminary, further studies need to be conducted to elucidate the real role of MSCs in patients affected with primary pulmonary pathological condition and SARS-CoV-2 infection.