TY - JOUR
KW - Adhesion
KW - Liver sinusoidal endothelial cells
KW - Migration
KW - immune cell
KW - organ-on-a-chip
AU - James I. Kennedy
AU - Scott P. Davies
AU - Peter W. Hewett
AU - Alex L. Wilkinson
AU - Ye H. Oo
AU - Wei-Yu Lu
AU - Alicia J. El Haj
AU - Shishir Shetty
AB - Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium.
BT - Frontiers in Cell and Developmental Biology
DA - 2024-04-17
DO - 10.3389/fcell.2024.1359451
LA - English
N2 - Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium.
PY - 2024
ST - Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells
T2 - Frontiers in Cell and Developmental Biology
TI - Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells: the potential for testing immunotherapies and cell therapy trafficking
UR - https://www.frontiersin.org/articles/10.3389/fcell.2024.1359451
VL - 12
Y2 - 2024-05-24
SN - 2296-634X
ER -