Heterogeneous expression of ACE2 and TMPRRS2 in mesenchymal stromal cells

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.

Keywords: adult stem cells; cellular therapy; mesenchymal stromal cells (MSCs); sars-CoV-2.

FIGURE 1

Heat map of RNA‐Seq transcriptome analysis for 22 selected genes. Log2 count values have been plotted onto heatmaps. The heatmap was drawn using pheatmap (pretty heatmaps) library using standard hclust R function for hierarchical clustering with euclidean distance measure and “complete” agglomeration method. Results of five MSCs donors per tissue source are displayed in green for AD‐MSC, in pink for BM‐MSCs and in blue for WJ‐MSCs

FIGURE 2

ACE2 and TMPRSS2 expression in human AD‐MSCs, BM‐MSCs and WJ‐MSCs. Relative expression by quantitative reverse transcription PCR (RT‐qPCR) of (A) ACE2 and (B) TMPRSS2 mRNA levels in AD‐MSCs (n = 5), BM‐MSCs (n = 5), and WJ‐MSCs (n = 5). Data are normalized with GAPDH. C, Representative Western blot of ACE2 and TMPRSS2 of the three different MSC types. D, Quantification showed a nearly no detectable expression of ACE2. E, Heterogenous expression of TMPRS2 in MSCs. Cell line Calu‐3 was used as a positive control. GAPDH was used as loading control for cell lysates