Abstract

3D Sprouting Lymph-angiogenesis Platform

Noo Li Jeon, Professor, Seoul National University

Formation of new lymphatic vessels, lymphangiogenesis, is central in diverse biological processes during development, inflammation and tumor metastasis. Currently there are no reliable models to recapitulate how sprouting lymphangiogenesis is initiated and coordinated. This presentation will describe a microfluidic platform optimized for reconstitution of lymphangiogenesis. With control over chemical and physical factors such as biochemical cues, interstitial flow (IF), and cell-cell interactions (endothelial-fibroblast), we found that coordinated effects of multiple factors are necessary for robust lymphatic sprouting in 3D extracellular matrix.  We observed that IF serves as an important cue that defines lymphangiogenic response and phenotypes of primary lymphatic endothelial cells. When combined with pro-lymphangiogenic factors, IF significantly increase and guide initiation and outgrowth of lymphatic sprouts toward upstream of the flow while suppressing downstream-directed sprouting. The lymphatic sprouts expressed molecular signatures and cellular phenotypes that closely approximate sprouting lymphatic neovessels in vivo, and reflected the modulatory effects of pro- and anti-lymphangiogenic stimuli.  Mechanical cue in the form of IF have profound effect on lymphangiogenic sprouting and thus the microfluidic platform provides a useful in-vitro model for investigation of lymphangiogenesis for organ-on-a-chip applications.