The development of new therapies is tremendously hampered by the insufficient availability of human model systems suitable for preclinical research on disease target identification, drug efficacy, and toxicity. Thus, drug failures in clinical trials are too common and too costly. Animal models or standard 2D in vitro tissue cultures, regardless of whether they are human based, are regularly not representative of specific human responses. Approaching near human tissues and organs test systems is the key goal of organs-on-chips (OoC) technology. This technology is currently showing its potential to reduce both drug development costs and time-to-market, while critically lessening animal testing. OoC are based on human (stem) cells, potentially derived from healthy or disease-affected patients, thereby amenable to personalized therapy development. It is noteworthy that the OoC market potential goes beyond pharma, with the possibility to test cosmetics, food additives, or environmental contaminants. This (micro)tissue engineering-based technology is highly multidisciplinary, combining fields such as (developmental) biology, (bio)materials, microfluidics, sensors, and imaging. The enormous potential of OoC is currently facing an exciting new challenge: emulating cross-communication between tissues and organs, to simulate more complex systemic responses, such as in cancer, or restricted to confined environments, as occurs in osteoarthritis. This review describes key examples of multiorgan/tissue-on-chip approaches, or linked organs/tissues-on-chip, focusing on challenges and promising new avenues of this advanced model system. Additionally, major emphasis is given to the translation of established tissue engineering approaches, bottom up and top down, towards the development of more complex, robust, and representative (multi)organ/tissue-on-chip approaches.
Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’