title: Systematic analysis of in vitro cell rolling using a multi-well plate microfluidic system.
abstract: A major challenge for cell-based therapy is the inability to systemically target a large quantity of viable cells with high efficiency to tissues of interest following intravenous or intraarterial infusion. Consequently, increasing cell homing is currently studied as a strategy to improve cell therapy. Cell rolling on the vascular endothelium is an important step in the process of cell homing and can be probed in-vitro using a parallel plate flow chamber (PPFC). However, this is an extremely tedious, low throughput assay, with poorly controlled flow conditions. Instead, we used a multi-well plate microfluidic system that enables study of cellular rolling properties in a higher throughput under precisely controlled, physiologically relevant shear flow. In this paper, we show how the rolling properties of HL-60 (human promyelocytic leukemia) cells on P- and E-selectin-coated surfaces as well as on cell monolayer-coated surfaces can be readily examined. To better simulate inflammatory conditions, the microfluidic channel surface was coated with endothelial cells (ECs), which were then activated with tumor necrosis factor-α (TNF-α), significantly increasing interactions with HL-60 cells under dynamic conditions. The enhanced throughput and integrated multi-parameter software analysis platform, that permits rapid analysis of parameters such as rolling velocities and rolling path, are important advantages for assessing cell rolling properties in-vitro. Allowing rapid and accurate analysis of engineering approaches designed to impact cell rolling and homing, this platform may help advance exogenous cell-based therapy.
authors.affiliation: Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital.
authors.forename: Oren
authors.initials: O
authors.lastname: Levy
authors.forename: Priya
authors.initials: P
authors.lastname: Anandakumaran
authors.forename: Jessica
authors.initials: J
authors.lastname: Ngai
authors.forename: Rohit
authors.initials: R
authors.lastname: Karnik
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Karp
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D019040:E-Selectin / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology; D005353:Fibronectins / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D019007:P-Selectin / Q000737:chemistry; D033081:Shear Strength; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry
chemical_list: D019040:E-Selectin; D005353:Fibronectins; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha