A safety consideration of mesenchymal stem cell therapy on COVID-19

Stem Cell Res. 2020 Dec:49:102066. doi: 10.1016/j.scr.2020.102066. Epub 2020 Oct 24.

Abstract

Due to the multi-potential differentiation and immunomodulatory function, mesenchymal stem cells (MSCs) have been widely used in the therapy of chronic and autoimmune diseases. Recently, the novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency but no effective drug is available to date. Several studies investigated MSCs therapy for COVID-19 patients. However, it remains unclear whether MSCs could be the host cells of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) and whether they might affect the SARS-CoV-2 entry into other cells. Here, we report that human MSCs barely express ACE2 and TMPRSS2, two receptors required for the virus endocytosis, indicating that MSCs are free from SARS-CoV-2 infection. Furthermore, we observed that MSCs were unable to induce the expression of ACE2 and TMPRSS2 in epithelial cells and macrophages. Importantly, under different inflammatory challenge conditions, implanted human MSCs failed to up-regulate the expression of ACE2 and TMPRSS2 in the lung tissues of mice. Intriguingly, we showed that a SARS-CoV-2 pseudovirus failed to infect MSCs and co-cultured MSCs did not increase the risk of SARS-CoV-2 pseudovirus infection in epithelial cells. All these results suggest that human MSCs have no risk of assisting SARS-CoV-2 infection and the use of MSCs as the therapy for COVID-19 patients is feasible and safe.

Keywords: ACE2; COVID-19; Mesenchymal stem cells; TMPRSS2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / biosynthesis
  • Animals
  • COVID-19 / transmission*
  • Cell Line
  • Heterografts
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells* / metabolism
  • Mesenchymal Stem Cells* / pathology
  • Mesenchymal Stem Cells* / virology
  • Mice
  • SARS-CoV-2 / metabolism*
  • Safety*
  • Serine Endopeptidases / biosynthesis

Substances

  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human