Heterogeneous expression of ACE2 and TMPRRS2 in mesenchymal stromal cells

J Cell Mol Med. 2022 Jan;26(1):228-234. doi: 10.1111/jcmm.17048. Epub 2021 Nov 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Angiotensin-Converting Enzyme 2 / genetics*
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • COVID-19 / genetics
  • COVID-19 / pathology
  • COVID-19 / therapy*
  • COVID-19 / virology
  • Cell- and Tissue-Based Therapy / methods*
  • Cytokine Release Syndrome / genetics
  • Cytokine Release Syndrome / pathology
  • Cytokine Release Syndrome / therapy*
  • Cytokine Release Syndrome / virology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Primary Cell Culture
  • Protein Binding
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / pathogenicity*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Umbilical Cord / cytology
  • Umbilical Cord / metabolism


  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human