Format

Send to

Choose Destination
Basic Res Cardiol. 2020 Jan 24;115(2):18. doi: 10.1007/s00395-020-0774-6.

Murine sca1/flk1-positive cells are not endothelial progenitor cells, but B2 lymphocytes.

Author information

1
Herzzentrum Bonn, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Germany. Eva.Steffen@ukbonn.de.
2
Herzzentrum Bonn, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Venusberg Campus 1, 53127, Bonn, Germany.
3
Krankenhaus der Barmherzigen Brüder, Innere Medizin III, Trier, Germany.
4
Westdeutsches Herz- und Gefäßzentrum, Klinik für Kardiologie und Angiologie, Universitätsklinikum Essen, Essen, Germany.
5
Cardiology Pasing, Munich, Germany.
6
University of the Saarland, Homburg, Saar, Germany.

Abstract

Circulating sca1+/flk1+ cells are hypothesized to be endothelial progenitor cells (EPCs) in mice that contribute to atheroprotection by replacing dysfunctional endothelial cells. Decreased numbers of circulating sca1+/flk1+ cells correlate with increased atherosclerotic lesions and impaired reendothelialization upon electric injury of the common carotid artery. However, legitimate doubts remain about the identity of the putative EPCs and their contribution to endothelial restoration. Hence, our study aimed to establish a phenotype for sca1+/flk1+ cells to gain a better understanding of their role in atherosclerotic disease. In wild-type mice, sca1+/flk1+ cells were mobilized into the peripheral circulation by granulocyte-colony stimulating factor (G-CSF) treatment and this movement correlated with improved endothelial regeneration upon carotid artery injury. Multicolor flow cytometry analysis revealed that sca1+/flk1+ cells predominantly co-expressed surface markers of conventional B cells (B2 cells). In RAG2-deficient mice and upon B2 cell depletion, sca1+/flk1+ cells were fully depleted. In the absence of monocytes, sca1+/flk1+ cell levels were unchanged. A PCR array focused on cell surface markers and next-generation sequencing (NGS) of purified sca1+/flk1+ cells confirmed their phenotype to be predominantly that of B cells. Finally, the depletion of B2 cells, including sca1+/flk1+ cells, in G-CSF-treated wild-type mice partly abolished the endothelial regenerating effect of G-CSF, indicating an atheroprotective role for sca1+/flk1+ B2 cells. In summary, we characterized sca1+/flk1+ cells as a subset of predominantly B2 cells, which are apparently involved in endothelial regeneration.

KEYWORDS:

Atherosclerosis; B Lymphocytes; Endothelial dysfunction; Endothelial progenitor cells; Endothelial regeneration

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center