Human mesenchymal stromal cells do not express ACE2 and TMPRSS2 and are not permissive to SARS-CoV-2 infection. (26th January 2021)

• Record Type: Journal Article
• Authors: Avanzini, Maria A.; Mura, Manuela; Percivalle, Elena; Bastaroli, Francesca; Croce, Stefania; Valsecchi, Chiara; Lenta, Elisa; Nykjaer, Giulia; Cassaniti, Irene; Bagnarino, Jessica; Baldanti, Fausto; Zecca, Marco; Comoli, Patrizia; Gnecchi, Massimiliano
• Is Part Of: Stem cells translational medicine. Volume 10:Number 4(2021)
• Page Start: 636
• Page End: 642
• Publication Date: 2021-01-26
• Subjects: adult stem cells -- angiotensin -- cellular therapy -- fetal stem cells -- mesenchymal stromal cells (MSCs); Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.20-0385
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: Anti-inflammatory and immune-modulatory therapies have been proposed for the treatment of COVID-19 and its most serious complications. Among others, the use of mesenchymal stromal cells (MSCs) is under investigation given their well-documented anti-inflammatory and immunomodulatory properties. However, some critical issues regarding the possibility that MSCs could be infected by the virus have been raised. Angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) are the main host cell factors for the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), entry, but so far it is unclear if human MSCs do or do not express these two proteins. To elucidate these important aspects, we evaluated if human MSCs from both fetal and adult tissues constitutively express ACE2 and TMPRSS2 and, most importantly, if they can be infected by SARS-CoV-2. We evaluated human MSCs derived from amnios, cord blood, cord tissue, adipose tissue, and bone marrow. ACE2 and TMPRSS2 were expressed by the SARS-CoV-2-permissive human pulmonary Calu-3 cell line but not by all the MSCs tested. MSCs were then exposed to SARS-CoV-2 wild strain without evidence of cytopathic effect. Moreover, we also excluded that the MSCs could be infected without showing lytic effects since their conditioned medium after SARS-CoV-2 exposure did not contain viral particles. Our data, demonstrating that MSCs derived from different human tissues are not permissive to SARS-CoV-2 infection, support the safety of MSCs as potential therapy for COVID-19. Abstract : SARS-CoV-2 enters into host cells through ACE2 and TMPRSS2. Mesenchymal stromal cells (MSCs) derived from amnios (A), cord blood (CB), cord tissue (CT), adipose tissue (AT) and bone marrow (BM) do not express these proteins, as demonstrated by RT-qPCR, western blot, ELISA and immunofuorescence. They are not infected by either spike pseudovirus, or by SARS-CoV-2 wild strain.