Heterogeneous expression of ACE2 and TMPRRS2 in mesenchymal stromal cells.

Debora Kehl,Debora Wanner,Melanie Generali,Simon P Hoerstrup,Michal J Okoniewski,Paolo Cinelli

doi:10.1111/jcmm.17048

Debora Kehl, Debora Wanner + Show 4 more

Open Access

https://doi.org/10.1111/jcmm.17048

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Abstract

The outbreak of COVID‐19 has become a serious public health emergency. The virus targets cells by binding the ACE2 receptor. After infection, the virus triggers in some humans an immune storm containing the release of proinflammatory cytokines and chemokines followed by multiple organ failure. Several vaccines are enrolled, but an effective treatment is still missing. Mesenchymal stem cells (MSCs) have shown to secrete immunomodulatory factors that suppress this cytokine storm. Therefore, MSCs have been suggested as a potential treatment option for COVID‐19. We report here that the ACE2 expression is minimal or nonexistent in MSC derived from three different human tissue sources (adipose tissue, umbilical cord Wharton`s jelly and bone marrow). In contrast, TMPRSS2 that is implicated in SARS‐CoV‐2 entry has been detected in all MSC samples. These results are of particular importance for future MSC‐based cell therapies to treat severe cases after COVID‐19 infection.

Highlights

The outbreak of COVID-19 has become a serious public health emergency
We report here that the angiotensinconverting enzyme 2 (ACE2) expression is minimal or nonexistent in Mesenchymal stem cells (MSCs) derived from three different human tissue sources
ACE2 and transmembrane protease serine 2 (TMPRSS2) are expressed on the cell surface of several human cells, for example, alveolar cells and capillary endothelium, but immune cells such as T and B lymphocytes are negative for ACE2.1

Summary

Introduction

The virus targets cells by binding the angiotensinconverting enzyme 2 (ACE2) receptor. Viral S-protein of SARS-CoV-2 binds ACE2 and utilizes membrane bound cell transmembrane protease serine 2 (TMPRSS2) to get primed and enter the human cells. ACE2 and TMPRSS2 are expressed on the cell surface of several human cells, for example, alveolar cells and capillary endothelium, but immune cells such as T and B lymphocytes are negative for ACE2.1. Even though in most coronavirus disease (COVID-19) patients, the disease progresses with a mild-to-moderate course in ca. In 14% of cases (especially high-risk patients), the disease can become lifethreatening leading to multiple organ failure and acute respiratory distress syndrome (ARDS) due to cytokine storm syndrome and dysregulated immune response.[2,3] In this subgroup, the mortality is significantly higher.

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