Human Mesenchymal Stromal Cells Are Resistant to SARS-CoV-2 Infection under Steady-State, Inflammatory Conditions and in the Presence of SARS-CoV-2-Infected Cells

Previous studies reported on the safety and applicability of mesenchymal stem/stromal cells (MSCs) to ameliorate pulmonary inflammation in acute respiratory distress syndrome (ARDS). Thus, multiple clinical trials assessing the potential of MSCs for COVID-19 treatment are underway. Yet, as SARS-inducing coronaviruses infect stem/progenitor cells, it is unclear whether MSCs could be infected by SARS-CoV-2 upon transplantation to COVID-19 patients. We found that MSCs from bone marrow, amniotic fluid, and adipose tissue carry angiotensin-converting enzyme 2 and transmembrane protease serine subtype 2 at low levels on the cell surface under steady-state and inflammatory conditions. We did not observe SARS-CoV-2 infection or replication in MSCs at steady state under inflammatory conditions, or in direct contact with SARS-CoV-2-infected Caco-2 cells. Further, indoleamine 2,3-dioxygenase 1 production in MSCs was not impaired in the presence of SARS-CoV-2. We show that MSCs are resistant to SARS-CoV-2 infection and retain their immunomodulation potential, supporting their potential applicability for COVID-19 treatment. •MSCs carry ACE2 and TMPRSS2 only at very low levels on the cell surface•Inflammatory conditions do not change ACE2 and TMPRSS2 expression on MSCs•MSCs are resistant to SARS-CoV-2 infection•MSCs retain their immunomodulation potential in the presence of SARS-CoV-2 Schäfer and colleagues found that human MSCs carry ACE 2 and TMPRSS2 at very low levels on the cell surface under steady-state and inflammatory conditions. Using their in vitro model for infection with SARS-CoV-2 from clinical isolates they show that MSC are resistant to SARS-CoV-2 infection and retain their immunomodulation potential supporting their potential applicability for COVID-19 treatment.