Characterization of a foetal liver cell population with endotelial engraftment potential in neonatal mice

Abstract

Mouse foetal liver (FL) hemato/vascular cells from day 12 of gestation (E12), expressing the Stem Cell Leukaemia (SCL)gene enhancer transgene (SCL-PLAP+ cells), had robust endothelial engraftment potential when transferred to the blood stream of newborns or adult conditioned recipients, compared to the scarce vascular contribution of adult bone marrow (BM) cells. We present data showing that long-term reconstituting endothelial cell (LTR-EC) activity is restricted to the SCLPLAP+ VE-cadherin+CD45- (P+V+C-) cell population, devoid of hematopoietic reconstitution activity and largely composed by Lyve1+ endothelial-committed cells. P+V+C- cells contributed to the liver sinusoidal endothelium and also to the heart, kidney and lung microvasculature. LTR-EC activity was detected at different stages of FL development, yet marginal activity was identified in the adult liver, revealing unknown functional differences between foetal and adult liver endothelial/endothelial progenitors. Importantly, the observations that expanding donorderived vascular grafts preferentially co-localize with proliferating hepatocyte-like cells and participate in the general circulation, support their functional integration in young livers. These findings offer new insights into the engraftment, phonotypical, and developmental characterization of a novel endothelial/endothelial progenitor cell subtype with multi-organ LTR-EC activity, potentially instrumental for the treatment/genetic correction of vascular diseases.