Personalised organs-on-chips: functional testing for precision medicine

Abstract

Organs-on-chips are microfluidic systems with controlled, dynamic microenvironments in which cultured cells exhibit functions that emulate organ-level physiology. They can in principle be 'personalised' to reflect individual physiology, for example by including blood samples, primary human tissue, and cells derived from induced pluripotent stem cell-derived cells, as well as by tuning key physico-chemical parameters of the cell culture microenvironment based on personal health data. The personalised nature of such systems, combined with physiologically relevant read-outs, provides new opportunities for person-specific assessment of drug efficacy and safety, as well as personalised strategies for disease prevention and treatment; together, this is known as 'precision medicine'. There are multiple reports of how to personalise organs-on-chips, with examples including airway-on-a-chip systems containing primary patient alveolar epithelial cells, vessels-on-chips with shapes based on personal biomedical imaging data and lung-on-a-chip systems that can be exposed to various regimes of cigarette smoking. In addition, multi-organ chip systems even allow the systematic and dynamic integration of more complex combinations of personalised cell culture parameters. Current personalised organs-on-chips have not yet been used for precision medicine as such. The major challenges that affect the implementation of personalised organs-on-chips in precision medicine are related to obtaining access to personal samples and corresponding health data, as well as to obtaining data on patient outcomes that can confirm the predictive value of personalised organs-on-chips. We argue here that involving all biomedical stakeholders from clinicians and patients to pharmaceutical companies will be integral to transition personalised organs-on-chips to precision medicine.

Fig. 1. Functional tests can be used to select, optimize or develop treatment options for patients. The tests are based on patient material and offer a functional read-out that is related to an aspect of patient outcome.

Fig. 2. Personalised organs-on-chips can emulate key aspects of a specific person. A, The bar on the left depicts how every individual has a profile of various aspects of their lifestyle, diet, physiology, genetics and environment that determines their predisposition for specific diseases and response to therapeutic interventions. Some of these aspects are unknown (grey), while some have been measured, and represented as ‘personal health data’. Examples are given in red, yellow, green, orange. On the right side, an similar bar depicts the aspects of a person's health data that can be controllably represented in an organ-on-chip system, thus making it ‘personalised’. Such personalised organs-on-chips can potentially be used to make person-specific predictions about disease prevention and treatment. B, Small airway-on-a-chip (left) can be subjected to defined ‘puff’ patterns of cigarette smoking via an automated system (middle), to which airway epithelium from COPD patients and healthy controls respond differently in terms of interleukin-8 (IL-8) release (right). Reproduced from Benam, et al. C, Computed tomography data of a coronary artery with and without stenosis (left) can be used to make personalised chips (middle) with unique flow profiles that determine dynamics of thrombosis when the chips are perfused with blood (right). Adapted from Costa, et al.

Fig. 3. Personalised organs-on-chips can be used to understand how particular health-related parameters affect functional outcome of an individual. Specific aspects like genetic variation (left), exposure to toxicants (middle) or grades of particular disease processes (right) can be systematically varied in different organs-on-chips while all other relevant and personalised aspects are held constant. This approach allows the ‘reverse engineering’ of the interactions that generate the functional outcome for an individual.