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.
Highlights
The first mention of immunology dates back to Ancient Greece [1]
Pasteur—who is considered the father of immunology—was the first to describe that bacteria could cause an infectious disease, which would be later known as germ theory
They designed a membrane-based perfusion bioreactor system containing: (1) an area for antigen-induced B-cell activation and dendritic cell (DC)–T-cell crosstalk supported by perfusable microporous hollow fibers, (2) a peripheral fluidic space to mimic the lymphatic drainage, and (3) a 3D hydrogel matrix loaded with dendritic cells (DCs) within two perfusable matrix sheets
Summary
The first mention of immunology dates back to Ancient Greece [1]. Thucydides described how there was no recurrence of the plague in those who already suffered from the disease in 430BC [2]. The organs involved in this system are mostly secondary lymphoid organs, such as the spleen, tonsils, lymph nodes (LNs) and the cutaneous and mucosal organs These are the organs where B- and T-lymphocytes recognize foreign antigens, initiate an effective immune response and help facilitate the crucial interactions between B- and T-cells. Giese et al developed so-called human artificial LNs (HuALN; Figure 3Ai,ii) that focused on the relationship between innate and adaptive immunity, the recognition of pathogens within the LN and the development of T-cell responses in vitro [44,45,46] They designed a membrane-based perfusion bioreactor system containing: (1) an area for antigen-induced B-cell activation and dendritic cell (DC)–T-cell crosstalk supported by perfusable microporous hollow fibers, (2) a peripheral fluidic space to mimic the lymphatic drainage, and (3) a 3D hydrogel matrix loaded with DCs within two perfusable matrix sheets. The human LN chip exhibited cytokine profiles similar to the human volunteers
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