Embryonic vasculogenesis by endothelial precursor cells derived from lung mesenchyme

During development, the lung mesenchyme has a dynamic relationship with the branching airway, Embryonic lung mesenchyme is loosely packed and composed of indistinguishable cells, yet it is the source of vascular progenitors t hat will become endothelial cells, smooth muscle cells and fibroblasts, In the lung, vessel development in the periphery proceeds first through vascul ogenesis, the migration and assembly of cells into a primitive network, and subsequently, through angiogenesis, the sprouting of vessels from this net work. As a way to assess the cellular and molecular mechanisms of lung vasc ularization, we have isolated and cloned cell lines from mouse fetal lung m esenchyme (MFLM). Two of these MFLM cell lines, MFLM-4 and MFLM-91U, displa y characteristics of an endothelial lineage. RNA analysis demonstrates tran scripts for the vascular endothelial growth factor receptors R1 and R2, the receptor tyrosine kinases, Tie-1 and Tie-2, as well as the Tie-2 ligands, Ang-1 and -2, The MFLM cell lines form extensive networks of capillary-like structures with lumens when cultured on a reconstituted basement membrane. In vivo, following blastocyst injection, the MFLM cells chimerize endothel ium of the lung and areas of the heart vasculature. The results from these studies suggest that MFLM-4 and MFLM-91U, derived from embryonic lung mesen chyme, can function in vitro and in vivo as endothelial precursors and as m odels of cardiopulmonary vascularization. (C) 2000 Wiley-Liss, Inc.