Using organ-on-chip related approaches for immune cell migration research

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Ren, Xiaoou
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Immune cell migration plays an essential role in immune surveillance and homeostasis maintenance. Misguided migratory responses of immune cells contribute to various pathological issues. Understand ing the mechanisms of immune cell migration is crucial and its investigation requires a suitable approach. Although various methods for cell migration study have been established, most of them lacking configuration of the complex microenvironment in vitro which makes the development of a suitable approach of vital importance. Organ-on-chip (OoC) approach can provide a better platform due to its ability to simulate the key features of certain tissues or organs. In this thesis, we developed different OoC related approaches to study disease-oriented immune cell migration. Specifically, we employed clinical samples in microfluidic device to simulate the microenvironment of chronic obstructive pulmonary disease (COPD), and demonstrated the usage of this approach to quantitatively investigate the complex migratory responses of T cells in COPD. Our results showed an inhibitory effect of the COPD sputum on T cell motility and chemotaxis, which may suggest a possible stopping mechanism to facilitate T cell accumulati on in the airway in COPD. We also mimicked the tumor microenvironment in vitro using primary murine natural killer (NK) cells and mouse tumor cell line (i.e., 4T1) in our microfluidic device, and demonstrated it as a proof of principle approach to study di rectional NK cell migration and NK cancer cell interactions in real-time. Furthermore, we developed a mimicked skin-on-chip (SoC) model that configured the key features of human skin and relevant chemical fields during cutaneous inflammation, and demonstrated its feasibility as a versatile tool for investigating T cell migration and screening potential drugs for targeting chemotactic signaling. Collectively, studies in this thesis bridge organ-specific applications with disease-oriented immune cell migration, and advance our knowledge on the complex roles of immune cell migration in specific disease conditions (i.e., COPD, cancer, skin inflammation), which provide a new conceptual and technological direction for immune cell migration research and contribute to the related research communities.
Immune cell migration, Microfluidics, Organ-on-chip approach, Microenvironment, Drug screening