Multidimensional Proteomic Approach of Endothelial Progenitors Demonstrate Expression of KDR Restricted to CD19 Cells

Abstract

Endothelial progenitor cells (EPCs) are involved in vasculogenesis and cardiovascular diseases. However, the phenotype of circulating EPCs remains elusive but they are more often described as CD34 + KDR + . The aim of the study was to extensively characterize circulating potential vasculogenic stem cell candidates in two populations of patients with cardiovascular disease by powerful multidimensional single cell complementary cytometric approaches (mass, imaging and flow). We identified cellular candidates in one patient before and after bioprosthetic total artificial heart implantation and results were confirmed in healthy peripheral and cord blood by mass cytometry. We also quantified cellular candidates in 10 patients with different COVID-19 severity. Both C-TAH implantation and COVID-19 at critical stage induce a redistribution of circulating CD34 + and CD19 + sub-populations in peripheral blood. After C-TAH implantation, circulating CD34 + progenitor cells expressed c-Kit stem marker while specific subsets CD34 + CD133 −/+ CD45 −/dim c-Kit + KDR − were mobilized. KDR was only expressed by CD19 + B-lymphocytes and CD14 + monocytes subpopulations in circulation. We confirmed by mass cytometry this KDR expression on CD19 + in healthy peripheral and cord blood, also with a VE-cadherin expression, confirming absence of endothelial lineage marker on CD34 + subtypes. In COVID-19, a significant mobilization of CD34 + c-Kit + KDR − cells was observed between moderate and critical COVID-19 patients regardless CD133 or CD45 expression. In order to better evaluate EPC phenotype, we performed imaging flow cytometry measurements of immature CD34 + KDR + cells in cord blood and showed that, after elimination of non-circular events, those cells were all CD19 + . During COVID-19, a significant mobilization of CD19 + KDR + per million of CD45 + cells was observed between moderate and critical COVID-19 patients regardless of CD34 expression. CD34 + c-Kit + cells are mobilized in both cardiovascular disease described here. KDR cells in peripheral blood are CD19 positive cells and are not classic vasculogenic stem and/or progenitor cells. A better evaluation of c-Kit and KDR expressing cells will lead to the redefinition of circulating endothelial progenitors. Graphical abstract Central illustration figure. Multidimensional proteomic approach of endothelial progenitors demonstrate expression of KDR restricted to CD19 cells. ...

No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

“…Notably, SARS-CoV-2 has not been found to enter red blood cells 44 . However, the possibility that BSG could act as an accessory binding receptor for the virus has been speculated in several publications to possibly explain in part the link between SARS-CoV-2 infection and hematological symptoms in patients 39 , 40 , 45 , 46 . Our data suggest this hypothesis should be treated cautiously.…”

Safety and Efficacy of Autologous Non-Hematopoietic Enriched Stem Cell Nebulization in Covid-19 Patients. A Randomized Clinical Trial, Abu Dhabi 2020.

“…Given that PB-NHESC-C is a product obtained from COVID-19 patients, the variability in the cellular number and phenotype is influenced by the immune response to viral infection and the mobilization of progenitor cells to damaged tissue. Therefore, these differences explain the differences found in this study between the severe and moderate groups [29]. Indeed, the significant CD5 dim cell count in the cellular preparation of moderate cases is synergically correlated with the absolute count of lymphocytes in peripheral blood, indicating their potential role as lymphocyte precursors.…”

“…The function of this marker has not been fully clarified, but it is associated with the inhibition or facilitation of adhesion, proliferation, and regulation of cell differentiation [34]. A significant increase in the peripheral blood of CD45 dim CD34 + cells in severe COVID -19 patients was reported [29] and interpreted as a response to endothelial regeneration during hypoxia. In our study, no relationship was found between the number of CD34 + cells in PB-NHESC-C and disease severity.…”

Usefulness of Plasma SARS-CoV-2 RNA Quantification by Droplet-based Digital PCR to Monitor Treatment Against COVID-19 in a B-cell Lymphoma Patient

“…Finally, with the development of recent therapies against COVID-19 such as immunomodulators like anti-IL-6R, mesenchymal stem cells therapy or convalescent COVID-19 plasmatherapy which have recently showed their efficacy to prevent clinical deterioration [ 4 ] or to cure [ 2 , 5 ] COVID-19, we particularly need specific biomarkers to monitor such treatments and SARS-CoV-2 RNAaemia by ddPCR seems to present such qualities in the global care of COVID-19.…”