Transdifferentiated Monocytes: a Novel Source of Lymphatic Endothelial-like Cells

Although monocytes have previously been demonstrated to contribute to lymphatic vessel formation in vivo, monocyte transdifferentiation into lymphatic endothelial cells and the specific conditions required remain unclear. In this study, monocyte cultures isolated from human peripheral blood were stimulated to transdifferentiate into lymphatic endothelial cells under specific in vitro induction conditions. These results demonstrate primary isolates of CD14 (+) monocytes express low levels of lymphatic endothelial cell specific markers or pan-endothelial markers under routine culture conditions. Using fibronectin (FN) coated flasks and EGM-2 supplemented culture medium, monocytes were induced to express lymphatic endothelial markers Prox-1, VEGFR-3, LYVE-1, Podoplanin, and pan-endothelial markers vWF, CD144, and VEGFR-2. Furthermore, using the FN/EGM-2/lipopolysaccharide (LPS) culture conditions, monocytes displayed dramatically increased expressions of Prox-1, VEGFR-3, Podoplanin, LYVE-1 and vWF, while the expression of CD144 and VEGFR-2 sharply decreased. In addition, VEGF-C secretion by monocytes exposed to fibronectin coated plates with EGM-2 medium with FN/EGM-2/LPS in vitro was significantly increased over levels seen in routine culture conditions. These findings demonstrate that monocytes can be induced to undergo transdifferentiation becoming more lymphatic endothelial-like cells and increase their VEGF-C production in an FN/EGM-2/LPS environment.