Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

Abstract

Understanding the immune system is of great importance for the development of drugs and the design of medical implants. Traditionally, two-dimensional static cultures have been used to investigate the immune system in vitro, while animal models have been used to study the immune system’s function and behavior in vivo. However, these conventional models do not fully emulate the complexity of the human immune system or the human in vivo microenvironment. Consequently, many promising preclinical findings have not been reproduced in human clinical trials. Organ-on-a-chip platforms can provide a solution to bridge this gap by offering human micro-(patho)physiological systems in which the immune system can be studied. This review provides an overview of the existing immune-organs-on-a-chip platforms, with a special emphasis on interorgan communication. In addition, future challenges to develop a comprehensive immune system-on-chip model are discussed.

Surface Modification of PDMS-Based Microfluidic Devices with Collagen Using Polydopamine as a Spacer to Enhance Primary Human Bronchial Epithelial Cell Adhesion

“…Organ-on-a-chip platforms can recapitulate the complexity of tissues and organs to some extent by combining cellular and extracellular cues in the chip. In addition to promising features such as providing tissue barriers and hydrodynamic forces that organ-on-a-chip devices offer, the inner surface of organ-on-a-chip devices can be coated with extracellular matrix (ECM) components to resemble the native cellular microenvironment and improve cellular adhesion [ 3 , 5 , 6 , 7 , 8 ].…”

The Peripheral Immune Landscape of Breast Cancer: Clinical Findings and In Vitro Models for Biomarker Discovery

“…Nonetheless, these models still reflect a much lower complexity compared to animal models, the current gold standard of mechanistic studies, pre-clinical testing, and biomarker discovery. Moving towards a research paradigm mostly based on human-only systems requires substantial technological advancements in the area of human immune modelling—ideally leading to the development of an “artificial immune system” built from modular units, each representing the function of an essential immune organ or compartment [ 165 , 196 ]. As of today, there are several reports on the development of advanced cellular models for lymph nodes [ 197 ], spleen [ 198 ], bone marrow [ 199 ], tonsil [ 161 ], thymus [ 200 ], and immunocompetent skin [ 201 ], lung [ 202 ], gut [ 203 ], and liver [ 204 ], albeit with varying levels of functionality and native-like architecture.…”

“…The generation of immune organ-like structures in vitro has been hampered by difficulties in recreating these very complex microenvironments, with uncommonly high cell densities and defined functional zones, on a small scale, and specific dynamics of cellular differentiation, communication and motility [ 165 , 205 ]. The field of microphysiological systems (MPS) (also known as “organs-on-chip”) combined with advancements on bioprinting can be instrumental in the development of novel advanced models that more closely resemble human tumor–immune interactions, and that allow the modular integration of several immune “organs” or compartments [ 165 , 196 , 206 ]. At the moment, the main challenge of this technology is the implementation of sensors for live monitoring of cellular processes, which can be based on the miniaturization of existing analytical techniques or in the integration of novel biosensors [ 207 ].…”

“…At the moment, the main challenge of this technology is the implementation of sensors for live monitoring of cellular processes, which can be based on the miniaturization of existing analytical techniques or in the integration of novel biosensors [ 207 ]. By bringing together the potential for broad customization of culture conditions, the advantage of miniaturization and throughput (compared with traditional bioreactors or culture plates), and the possibility of replicating different biological compartments of the TME in the same system [ 208 , 209 ], MPS technology may be a starting platform to refocus on basic and applied human immunology research [ 165 , 196 ].…”

Potential Application of Plant-Based Functional Foods in the Development of Immune Boosters

“…NK cells express several activation and inhibitory receptors, and secrete cytokines and chemokines to enable interaction with other immune cells (Vivier et al, 2018). Additionally, NK cells play a key role in tumor immune surveillance, generating a coordinated anti-tumor immune response through their cytotoxic effect function and their ability to interact with other immune cells (Morsink et al, 2020). Regulation of the activity of NK cells can strengthen the immune system against diseases.…”