Abstract
The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) 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 angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.
Highlights
congenital pulmonary airway malformations (CPAM) is a congenital disease characterized by abnormal airway defects during fetal lung development, and it is characterized by cyst formation
Jurkat cells, where Bid was cleaved in a Caspase-10 dose-dependent manner [54]. These results suggest that SARS-CoV-2 exposure did not seem to affect the cell cycle or apoptosis in mesenchymal stromal cells (MSCs)-lung
One sample was derived from the cyst wall (MSCs-CPAM), while the other one was taken from a “healthy” section
Summary
Cell-based therapy was proposed as a treatment for respiratory system diseases, and encouraging results have been reported following mesenchymal stromal cells (MSCs) infusion [3] Due to their capacity to produce and secrete a variety of paracrine factors and bioactive macro-molecules and their immunomodulatory effects, they are considered key players in lung tissue injury and function repair. ACE2− MSCs, preventing the release of cytokines by the immune system and promoting endogenous repair due to their regenerative properties, are proposed as valid candidates for the therapy of patients with COVID-19. This encourages future investigation in order to establish the efficacy of this therapeutic modality in lung diseases [7]
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