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Isolation of Human Lymphatic Endothelial Cells by Multi-parameter Fluorescence-activated Cell Sorting
Published on: May 1, 2015
Embryonic development and malformation of lymphatic vessels
Jörg Wilting1, Kerstin Buttler, Jochen Rössler
1Department of Pediatrics 1, Georg-August-University, Goettingen, Germany.
Novartis Foundation Symposium
|February 28, 2008
Summary
Lymphatic endothelial cells (LECs) originate from dual sources in embryos, a venous and a mesenchymal origin. This dual origin may explain lymphatic malformations like lymphangiomas in children.
Area of Science:
- Developmental Biology
- Vascular Biology
- Human Pathology
Background:
- Lymphatic vessel malformations, including lymphangiectasia, lymphangioma, and lymphangiomatosis, affect 1.2-2.8 per thousand individuals.
- The etiology of these malformations is unknown, and effective causal therapies are lacking.
Purpose of the Study:
- To investigate the origin of lymphatic endothelial cells (LECs) in avian and murine embryos.
- To compare the molecular profiles of LECs from normal and malformed lymphatic vessels in children.
Main Methods:
- Cell lineage tracing in avian embryos to determine the origin of the jugular lymph sac (JLS).
- Analysis of LEC precursors in murine embryos using markers like Lyve1 and CD45.
- Microarray analysis of LECs from pediatric lymphangiomas to identify regulated genes, including VEGFR3.
Main Results:
- In avian embryos, the JLS is of venous origin, while dermal lymphatics originate from mesenchymal lymphangioblasts, suggesting a dual LEC origin.
- Murine embryos show LEC precursors in both cardinal veins and mesenchyme, with mesenchymal cells exhibiting both lymphatic and leukocyte markers (CD45).
- Microarray analysis revealed significant gene regulation in pediatric lymphangioma LECs, notably VEGFR3.
Conclusions:
- LECs in avian and potentially murine embryos have a dual origin: venous and mesenchymal.
- Mesenchymal LEC precursors may share characteristics with leukocytes, potentially linking to conditions like Kaposi's sarcoma in humans.
- VEGF receptor 3 (VEGFR3) may play a role in the development of lymphangiomas.
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