Microfluidic In Vitro Model of Lymphatic Metastasis

Abstract

Lymphatic vessels are closely involved in various diseases including inflammation and metastasis. However, elucidating the mechanisms of lymphatic function in physiological and pathological condition has been hampered by lack of reliable in vitro model recapitulating the complex in vivo environment of lymphatic vessels. In this study, a microfluidic platform that reconstitutes the three-dimensional lymphatic vascular network with luminal accessibility is presented. Fibroblasts together with pro-lymphangiogenic factors successfully supported the development of vascular network from primary human lymphatic endothelial cells. The vascular formation was further promoted by the appropriate speed of flow induced by hydrostatic pressure difference. The vascular network was perfused only when LECs were patterned separately with fibroblasts and flow was applied. The perfused network exhibited basic characteristics of in vivo lymphatic vessels, and it was maintained intact at least for 5 days only with basal medium. After vessel perfusion, cancer cells introduced into the device moved into the vascular network and stably adhered to the inside of vessels. This study provides a biomimetic 3D in vitro model that allows for studying the function of lymphatic endothelium in cancer metastasis and immune response.