Human Organoids and Organs‐on‐Chips for Addressing COVID‐19 Challenges

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to our lives. Although animal models and monolayer cell cultures are utilized for pathogenesis studies and the development of COVID-19 therapeutics, models that can more accurately reflect human-relevant responses to this novel virus are still lacking. Stem cell organoids and bioengineered organs-on-chips have emerged as two cutting-edge technologies used to construct biomimetic in vitro three-dimensional (3D) tissue or organ models. In this review, the key features of these two model systems that allow them to recapitulate organ physiology and function are introduced. The recent progress of these technologies for virology research is summarized and their utility in meeting the COVID-19 pandemic is highlighted. Future opportunities and challenges in the development of advanced human organ models and their potential to accelerate translational applications to provide vaccines and therapies for COVID-19 and other emerging epidemics are also discussed.

In vitro high-content tissue models to address precision medicine challenges

“…The use of in vitro tissue models has advanced into organ-on-a-chip models where cutting-edge 3D microtissues are combined with microscale fluids that allow for the temporal and spatial control of cellular microenvironments and the manipulation of small amounts of fluids ( Low et al, 2021 ; Meyvantsson and Beebe, 2008 ). In other words, organ-on-a-chip models are microphysiological systems encompassing microfluidic devices combined with dynamic cell cultures to mimic tissue and organ systems ( Esch et al, 2015 ; Wang et al, 2022 ; Wang et al, 2021b ; Zhang et al, 2018 ). This strategy would mimic and translate the structure, function, physiology, and pathology of human organs in a better way, into practical in vitro models, and overcoming some key limitations of current planar or static in vitro models and animal models ( Sasmal et al, 2018 ).…”

Brain organoids for addressing COVID-19 challenge

“…With fluid flow, stretch, and tissue interface to mimic cellular microenvironment on a bioengineered microfluidic cell culture device, recapitulating the brain organoid-on-a-chip ( Park et al, 2019 ). (B) Integrating brain organoid and other organoids with other approaches like multi-omics, biosensors, 3D bioprinting, and artificial intelligence to generate multi-organoid-on-chips to provide new pathway for virus, which physiologically relevant model systems can be applied to study SARS-CoV-2 virus transmission, pathogenesis and tropism, host-virus interactions, immune responses, and screen preclinical drugs and vaccine ( Sang et al, 2021 ; Wang et al, 2022 ).…”

“…Therefore, we introduced the organoid-on-chips technology, which is a micro-physiological system built on a chip with microfluidics as its core, 2 https://organovir.com through the cross-fertilization of physics, chemistry, biology, materials science, engineering, micro-electro-mechanics and medicine, and other multidisciplinary science and technology fields (Reardon, 2015;Park et al, 2019). Organoid-on-chips technology is included in organ-on-chips technology, which replaces 2D cells with organoids and uses microfluidics to construct a unified whole in vitro to represent multiple organoids, biofluids, mechanical signals, and functional tissue interfaces (Wang et al, 2022). The use of this model allows for a more comprehensive understanding of the association between viruses and neurological manifestations based on existing findings, providing a new platform for discovering potential targets and developing effective treatments.…”

Emerging toolset of three-dimensional pulmonary cell culture models for simulating lung pathophysiology towards mechanistic elucidation and therapeutic treatment of SARS-COV-2 infection

“…In addition, a computer-controlled vacuum in these chambers can be used to produce cyclic strain ranging from 5% to 15% to match normal levels of strain to mimic physiopathological breathing movements ( Birukov et al, 2003 ). Therefore, organ-on-a-chip can manipulate not only biochemical factors (such as cytokines, oxygen, and nutrients) but also dynamic physical factors (such as shear stress and cyclic strain), both of which are critical in understanding lung organ-level functions and permit researchers to mimic disease pathogenesis of COVID-19 ( Huh et al, 2010 ; Benam et al, 2016 ; Novak et al, 2021 ; Wang et al, 2022 ).…”