Dodging COVID-19 infection: low expression and localization of ACE2 and TMPRSS2 in multiple donor-derived lines of human umbilical cord-derived mesenchymal stem cells

Abstract

Background Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have immunomodulatory properties that are of interest to treat novel coronavirus disease 2019 (COVID-19). Leng et al. recently reported that hUC-MSCs derived from one donor negatively expressed Angiotensin-Converting Enzyme 2 (ACE2), a key protein for viral infection along with Transmembrane Serine Protease 2 (TMPRSS2). The purpose of this study was to quantify the expression of ACE2 and TMPRSS2 in hUC-MSCs lots derived from multiple donors using molecular-based techniques in order to demonstrate their inability to be a host to SARS-CoV-2. Methods Expression of ACE2 and TMPRSS2 was analyzed in 24 lots of hUC-MSCs derived from Wharton's jelly via quantitative polymerase chain reaction (qPCR), Western Blot, immunofluorescence and flow cytometry using 24 different donors. Results hUC-MSCs had significantly lower ACE2 (p = 0.002) and TMPRSS2 (p = 0.008) expression compared with human lung tissue homogenates in Western blot analyses. Little to no expression of ACE2 was observed in hUC-MSC by qPCR, and they were not observable with immunofluorescence in hUC-MSCs cell membranes. A negative ACE2 and TMPRSS2 population percentage of 95.3% ± 15.55 was obtained for hUC-MSCs via flow cytometry, with only 4.6% ACE2 and 29.5% TMPRSS2 observable positive populations. Conclusions We have demonstrated negative expression of ACE2 and low expression of TMPRSS2 in 24 lots of hUC-MSCs. This has crucial implications for the design of future therapeutic options for COVID-19, since hUC-MSCs would have the ability to “dodge” viral infection to exert their immunomodulatory effects.

Stem Cells Therapy for COVID-19: A Systematic Review and Meta-Analysis

“…Avanzini et al ( 35 ) and Schäfer et al ( 36 ) in their in vitro studies found that both fetal and adult MSCs have a deficient expression of ACE2 and TMPRSS2. Hernandez et al ( 37 ) reported the same result in human UC-MSCs. However, Desterke et al ( 38 ) reported that adult MSCs express ACE2 highly, while placenta-derived MSCs express ACE2 at a low level and only in initial passages of cultures.…”

Mesenchymal stem/stromal cell–based therapies for COVID-19: First iteration of a living systematic review and meta-analysis

“…Another study demonstrated that AT-MSCs have more potent immunomodulatory properties and exhibit greater IDO production compared to BM-MSCs ( 73 ). For the treatment of COVID-19 it may be important to select tissue sources that yield MSCs with reduced expression or lack of the ACE2 receptor ( 74 , 75 ). This could allow MSCs to persist longer following administration in patients with COVID-19.…”

Mesenchymal Stem Cell-Based COVID-19 Therapy: Bioengineering Perspectives

“…However, reported data is variable. In such a study, MSCs were reported to lack ACE2 and TMPRRS2 expressions [69][70][71], while other studies showed that ACE2 was highly expressed in MSCs derived from adult bone marrow, adipose tissue or umbilical cord [72,73]. Some studies also showed that ACE2 expression provides protective roles to MSCs against SARS-CoV-2 infection [74,75].…”