title: Endothelial progenitor cell recruitment in a microfluidic vascular model.
abstract: During vessel injury, endothelial progenitors cells (EPCs) are recruited from bone marrow and directed to the hypoxic injury site. The hypoxic conditions in the damaged blood vessel promote TNF-α, which upregulates intercellular adhesion molecule-1 (ICAM-1). EPCs attach to endothelial cell lining using ICAM-1. Here we aimed to examine EPC attachment to ECs in an injured-blood vessel conditions. We first determined ICAM-1 expression in stimulated HUVECs. We stimulated HUVECs with 21% oxygen (atmospheric), atmospheric with TNF-α-supplemented media, 1% oxygen (hypoxia), and hypoxia with TNF-α-supplemented media and found the highest ECFC attachment on HUVECs stimulated with TNF-α and hypoxia, correlating with the highest ICAM-1 expression. We next designed, fabricated and tested a three-dimensional microbioreactor (3D MBR) system with precise control and monitoring of dissolve oxygen and media flow rate in the cellular environment. We utilized a step-wise seeding approach, producing monolayer of HUVECs on all four walls. When stimulated with both TNF-α and hypoxia, ECFC retention on HUVECs was significantly increased under low shear stress compared to static controls. Overall, the 3D MBR system mimics the pathological oxygen tension and shear stress in the damaged vasculature, providing a platform to model vascular-related disorders.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences Oncology Center and Institute for NanoBioTechnology, The Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Lewis
authors.forename: Hasan E
authors.initials: HE
authors.lastname: Abaci
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Sharon
authors.initials: S
authors.lastname: Gerecht
mesh_terms: D019149:Bioreactors; D002448:Cell Adhesion / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003198:Computer Simulation; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D044085:Microfluidics / Q000379:methods*; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D010100:Oxygen