title: Engineering of a Biomimetic Pericyte-Covered 3D Microvascular Network.
abstract: Pericytes enveloping the endothelium play an important role in the physiology and pathology of microvessels, especially in vessel maturation and stabilization. However, our understanding of fundamental pericyte biology is limited by the lack of a robust in vitro model system that allows researchers to evaluate the interactions among multiple cell types in perfusable blood vessels. The present work describes a microfluidic platform that can be used to investigate interactions between pericytes and endothelial cells (ECs) during the sprouting, growth, and maturation steps of neovessel formation. A mixture of ECs and pericytes was attached to the side of a pre-patterned three dimensional fibrin matrix and allowed to sprout across the matrix. The effects of intact coverage and EC maturation by the pericytes on the perfused EC network were confirmed using a confocal microscope. Compared with EC monoculture conditions, EC-pericyte co-cultured vessels showed a significant reduction in diameter, increased numbers of junctions and branches and decreased permeability. In response to biochemical factors, ECs and pericytes in the platform showed the similar features with previous reports from in vivo experiments, thus reflect various pathophysiological conditions of in vivo microvessels. Taken together, these results support the physiological relevancy of our three-dimensional microfluidic culture system but also that the system can be used to screen drug effect on EC-pericyte biology.
authors.affiliation: Division of WCU Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jaerim
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Minhwan
authors.initials: M
authors.lastname: Chung
authors.affiliation: School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sudong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences and Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Jo
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Biomedical Sciences and Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, Republic of Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of WCU Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea; School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea; Institute of Advanced Machinery and Design, Seoul National University, Seoul, Republic of Korea.
authors.forename: Noo Li
authors.initials: NL
authors.lastname: Jeon
mesh_terms: D032701:Biomimetics; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D055806:Microvessels / Q000166:cytology*; D020286:Pericytes / Q000166:cytology*; D023822:Tissue Engineering