Application of lung microphysiological systems to COVID-19 modeling and drug discovery: a review

Abstract

There is a pressing need for effective therapeutics for coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The process of drug development is a costly and meticulously paced process, where progress is often hindered by the failure of initially promising leads. To aid this challenge, in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening, thereby saving valuable time and resources during a pandemic crisis. The SARS-CoV-2 virus attacks the lung, an organ where the unique three-dimensional (3D) structure of its functional units is critical for proper respiratory function. The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types. Current model systems include Transwell, organoid and organ-on-a-chip or microphysiological systems (MPSs). We review models that have direct relevance toward modeling the pathology of COVID-19, including the processes of inflammation, edema, coagulation, as well as lung immune function. We also consider the practical issues that may influence the design and fabrication of MPS. The role of lung MPS is addressed in the context of multi-organ models, and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

Post-COVID Syndrome: The Research Progress in the Treatment of Pulmonary sequelae after COVID-19 Infection

“…Organoids are three-dimensional tissue cultures resulting from pluripotent or induced pluripotent stem cells (PSC/iPSC) that self-organize spatially in a similar way to their in vivo counterparts. Stem cells are seeded on collagen suspended clusters or ECM solution such as Matrigel (an ECM isolated from Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells) with the addition of appropriate growth factors for differentiation into the lineage of interest [112].…”

“…Further limitations are due to the lack of vascularization and air-liquid interface, without taking into account the high variability of organoids in terms of size and cellular composition [112].…”

“…Therefore, this microfluidic technology allows the reproduction of cellular interactions in a vascularized environment, closely mimicking the function of the organ (Figure 4) [112].…”

An Immunocompetent Microphysiological System to Simultaneously Investigate Effects of Anti-Tumor Natural Killer Cells on Tumor and Cardiac Microtissues

“…Currently developed MPSs can interconnect up to ten organ models for an experimental duration of up to four weeks ( 16 , 17 ), making them suitable systems for systemic investigations of inter-tissue communication and for therapeutic testing. A wide range of single- or multi-tissue MPSs have been developed, among which are lung MPSs ( 18 ), gastrointestinal MPSs ( 19 ), liver MPSs ( 20 ), and immunocompetent MPSs (iMPSs).…”

Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives

“…The recent advances in organ-on-chips and MOCs technologies have been extensively reviewed in the literature, providing a thorough insight into the development of microphysiological systems resembling the liver and heart [24], intestine [25], lung [26], kidney [27], and multi-organ [2,[28][29][30][31] functions for drug discovery and drug toxicity screening applications. Driven by the momentum of MOCs technologies, the current review will cover the latest advancements and challenges encountered in the field of MOC systems and the essential parameters for their successful and timely commercialization.…”