Developmentally inspired human 'organs on chips'

Abstract

Although initially developed to replace animal testing in drug development, human 'organ on a chip' (organ chip) microfluidic culture technology offers a new tool for studying tissue development and pathophysiology, which has brought us one step closer to carrying out human experimentation in vitro In this Spotlight article, I discuss the central role that developmental biology played in the early stages of organ-chip technology, and how these models have led to new insights into human physiology and disease mechanisms. Advantages and disadvantages of the organ-chip approach relative to organoids and other human cell cultures are also discussed.

Keywords: Mechanical; Mechanobiology; Microfluidic; Multiphysiological system; Organoid; ‘Organ on a chip’.

Fig. 1.

A multi-channel human organ-chip model of the lung alveolus. (A) The lung chip is made of an optically clear, flexible, silicone rubber polymer the size of a computer memory stick with two tiny hollow channels running parallel along its length separated by a flexible porous membrane of the same material (channels are filled with blue and yellow dyes). (B) Diagrammatic cross-sections of the lung chip showing how living human alveolar epithelium is cultured on top of the porous membrane, which is coated with ECM, and air (blue) is introduced into the overlying space to create an air-liquid interface, while human microvascular endothelium is grown on the opposite side of the same membrane under continuous medium flow (red). These two channels are also surrounded on both sides by hollow vacuum chambers through which cyclic suction is applied (left image) and released (right image) to mimic breathing motions by rhythmically extending and relaxing the flexible porous membrane and attached lung tissues. In this manner, this device essentially creates a living, breathing, 3D cross-section of a major functional unit of a living human organ – the lung alveolus. A similar approach can be applied to model major functional units of other human organs.