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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1214-1216.
Prepublished online as a Blood First Edition Paper on September 29, 2005; DOI 10.1182/blood-2005-08-3400.
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Submitted August 23, 2005
Accepted September 22, 2005
Induction of lymphatic endothelial cell differentiation in embryoid bodies
Ruediger Liersch, Filip Nay, Lingge Lu, and Michael Detmar*
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
* Corresponding author; email: michael.detmar{at}pharma.ethz.ch.
The molecular mechanisms that regulate the formation of the lymphatic vascular system remain poorly characterized. Whereas studies in embryonic stem (ES) cells have provided major new insights into the mechanisms of blood vessel formation, development of lymphatic endothelium has not been previously observed. We established embryoid bodies (EBs) from murine ES cells, in the presence or absence of lymphangiogenic growth factors. We found that lymphatic endothelial cells develop at day 18 after EB formation. These cells express CD31 and the lymphatic lineage markers Prox-1 and Lyve-1, but not the blood vascular marker MECA-32, and frequently sprout from preexisting blood vessels. Lymphatic vessel formation was potently promoted by VEGF-A and VEGF-C, but not bFGF. Our results reveal - for the first time - that ES cells can differentiate into lymphatic endothelial cells, and identify the EB assay as powerful new tool to dissect the molecular mechanisms that control lymphatic vessel formation.
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