Functional integration of natural killer cells in a microfluidically perfused liver on-a-chip model

BMC Research Notes

Research Note

Utz Settmacher¹  René Fahrner²  Marko Gröger³  Alexander S. Mosig³ 

[1] Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747, Jena, Germany;Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747, Jena, Germany;Department of Vascular Surgery, University Hospital Bern, University of Bern, 3010, Bern, Switzerland;Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07747, Jena, Germany;Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07747, Jena, Germany;

关键词: Natural killer cells;    NKp46;    Liver;    Microfluidic;    Liver-on-a-chip;    Cytokines;   

DOI  :  10.1186/s13104-023-06575-w

 received in 2023-06-10, accepted in 2023-10-13,  发布年份 2023

来源: Springer

【 摘 要 】

ObjectiveThe liver acts as an innate immunity-dominant organ and natural killer (NK) cells, are the main lymphocyte population in the human liver. NK cells are in close interaction with other immune cells, acting as the first line of defense against pathogens, infections, and injury.A previously developed, three-dimensional, perfused liver-on-a-chip comprised of human cells was used to integrate NK cells, representing pivotal immune cells during liver injury and regeneration. The objective of this study was to integrate functional NK cells in an in vitro model of the human liver and assess utilization of the model for NK cell-dependent studies of liver inflammation.ResultsNK cells from human blood and liver specimen were isolated by Percoll separation with subsequent magnetic cell separation (MACS), yielding highly purified blood and liver derived NK cells. After stimulation with toll-like-receptor (TLR) agonists (lipopolysaccharides, Pam3CSK4), isolated NK cells showed increased interferon (IFN)-gamma secretion. To study the role of NK cells in a complex hepatic environment, these cells were integrated in the vascular compartment of a microfluidically supported liver-on-a-chip model in close interaction with endothelial and resident macrophages. Successful, functional integration of NK cells was verified by immunofluorescence staining (NKp46), flow cytometry analysis and TLR agonist-dependent secretion of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Lastly, we observed that inflammatory activation of NK cells in the liver-on-a-chip led to a loss of vascular barrier integrity. Overall, our data shows the first successful, functional integration of NK cells in a liver-on-a-chip model that can be utilized to investigate NK cell-dependent effects on liver inflammation in vitro.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 1

Fig. 3

Fig. 2

12936_2017_2014_Article_IEq61.gif