Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability

• Published in: PloS one Vol. 10; no. 9; p. e0137301
• Main Authors: Sato, Miwa, Sasaki, Naoki, Ato, Manabu, Hirakawa, Satoshi, Sato, Kiichi, Sato, Kae
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.09.2015; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Assaying; Blood; Blood vessels; Blood-brain barrier; Cadherins; Cancer therapies; Capillary Permeability; Cattle; Cell culture; Cell junctions; Cells, Cultured; Coculture Techniques; Drug delivery systems; Endothelial cells; Endothelium, Vascular - cytology; Experiments; Histamine; Histamine - pharmacology; Humans; Inflammation; Lab-On-A-Chip Devices; Localization; Lymphatic system; Lymphatic vessels; Lymphatic Vessels - cytology; Lymphatic Vessels - physiology; Medical imaging; Methods; Microcirculation; Microfluidics; Permeability; Permeability coefficient; Physiological aspects; Physiology; Polyethylene terephthalate; Proteins; Rodents; Science; Studies; Thrombosis; Tomography; Venom; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0137301

We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs) and lymphatic endothelial cells (LECs) were cocultured back-to-back. At cell-cell junctions of both BECs and LECs, claudin-5 and VE-cadherin were detected. The permeability coefficient measured here was lower than the value reported for isolated mammalian venules. Moreover, our results showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and that treatment with histamine, an inflammation-promoting substance, induced changes in the localization of tight and adherens junction-associated proteins and an increase in vascular permeability in the microdevice. These findings indicated that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform. Using this microcirculation device, the vascular damage induced by habu snake venom was successfully assayed, and the assay time was reduced from 24 h to 30 min. This is the first report of a microcirculation model in which BECs and LECs were cocultured. Because the micromodel includes lymphatic vessels in addition to blood vessels, the model can be used to evaluate both vascular permeability and lymphatic return rate.