Murine sca1/flk1-positive cells are not endothelial progenitor cells, but B2 lymphocytes
Open Access
- 24 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Basic Research in Cardiology
- Vol. 115 (2), 1-12
- https://doi.org/10.1007/s00395-020-0774-6
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.Funding Information
- Bonfor Bonn
This publication has 48 references indexed in Scilit:
- B Cells Promote Tumor Progression via STAT3 Regulated-AngiogenesisPLOS ONE, 2013
- Critical Reevaluation of Endothelial Progenitor Cell Phenotypes for Therapeutic and Diagnostic UseCirculation Research, 2012
- Acrolein Inhalation Prevents Vascular Endothelial Growth Factor–Induced Mobilization of Flk-1 + /Sca-1 + Cells in MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2011
- Endothelial progenitor cells: Quo Vadis?Journal of Molecular and Cellular Cardiology, 2011
- Synergistic effects of telmisartan and simvastatin on endothelial progenitor cellsJournal of Cellular and Molecular Medicine, 2010
- B Cell-Derived Vascular Endothelial Growth Factor A Promotes Lymphangiogenesis and High Endothelial Venule Expansion in Lymph NodesThe Journal of Immunology, 2010
- Endothelial-Regenerating CellsHypertension, 2010
- CD19+CD24hiCD38hi B Cells Exhibit Regulatory Capacity in Healthy Individuals but Are Functionally Impaired in Systemic Lupus Erythematosus PatientsImmunity, 2010
- Endothelial progenitor cells in health and atherosclerotic diseaseAnnals of Medicine, 2007
- Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular EventsCirculation, 2005