ImmunoSensation - the immune sensory system

Basic Res Cardiol. 2020 Jan 24.

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

Steffen E, Mayer von Wittgenstein WBE, Hennig M, Niepmann ST, Zietzer A, Werner N, Rassaf T, Nickenig G, Wassmann S, Zimmer S, Steinmetz M

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.

PMID: 31980946