Characterization of a Fetal Liver Cell Population Endowed with Long-Term Multiorgan Endothelial Reconstitution Potential

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This publication (Cañete A. et al, Stem Cells, 2016) represents a key step in our collaborative research activity dedicated to characterize cell subsets within the murine fetal liver endowed with vascular endothelial engraftment potential when transplanted into newborn mice. In previous work we have characterized the 3’ enhancer derived from the Stem Cell Leukaemia (SCL) gene as an optimal marker for HSCs, also active in vascular endothelial cells (Silberstein L. et al, Stem Cell, 2005). We used this key enhancer activity as a tool to both select cell progenitors from the FL and trace their endothelial lineage upon transplantation. We found that fetal liver-derived SCL-3’Enh+ cells presented a strong vascular endothelial engraftment activity in different organs (Garcia-Ortega M. et al, Stem Cell, 2010). The next question was to determine the cell subset within the SCL-3’Enh+ cell pool that presented endothelial engraftment potential. Base on previous reports on the multi-organ endothelial engraftment potential of adult bone marrow derived HSCs, we speculated that fetal liver HCS could be the responsible population. We could not confirm this hypothesis and concluded that fetal HSCs have very little, if an, endothelial differentiation potential in our transplantation model. Interestingly, we identified a new endothelial progenitor/endothelial cell population characterized as SCL-3’Enh+Ve-cad+CD45-Lyve1+/- , responsible for the strong, long term reconstituting endothelial cell (LTR-EC) activity, devoid of hematopoietic engraftment potential. This cell population is almost restricted to the fetal liver, emerges at day 11 of development and it is not detected in the adult liver. Future studies will focus on understanding the mechanisms underling the unique engraftment properties the SCL-3’Enh+Ve-cad+CD45-Lyve1+/- population, potential cooperation with fetal-derived hematopoietic cells and explore cell therapeutic applications on re-vascularization of targeted organs, with a particular focus in the liver and heart.

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