Biomimetic Human Disease Model of SARS‐CoV‐2‐Induced Lung Injury and Immune Responses on Organ Chip System

Zhang, Min; Wang, Peng; Luo, Rong-Hua; Wang, Yaqing; Li, Zhongyu; Guo, Yaqiong; Yao, Yudong; Li, Minghua; Tao, Tingting; Chen, Wenwen; Han, Jian; Liu, Haitao; Cui, Kaifeng; Zhang, Xu; Zheng, Yong‐Tang; Qin, Jianhua

doi:10.1002/advs.202002928

Cited by 149 publications

(186 citation statements)

References 54 publications

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“…Portfolios of primary cell lines are also available, informing drug bioavailability in multiple susceptible cell types that may contribute to pathology and disease in humans 49,52 . Major advances in human organ-on-a-chip and stem cell research have also occurred over the past two decades, affording relevant primary human tissues from different organs that are infected by RNA viruses [53][54][55] . For greatest efficacy, initial screening should be carried out in primary cell lines; greater expense and effort will be offset by increased relevance and a greater likelihood that hits will be successful, especially for host-targeted therapeutics.…”

Section: Development Of Critical Tools and Methodsmentioning

confidence: 99%

Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases

Meganck

Baric

2021

Nat Med

180

161

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The twenty-first century has already recorded more than ten major epidemic or pandemic virus emergence events, including the ongoing and devastating coronavirus disease 2019 (COVID-19) pandemic. As viral disease emergence is expected to accelerate, these data dictate a need for proactive approaches to develop broadly active family-specific and cross-family therapeutics for use in future disease outbreaks. Emphasis should focus not only on the development of broad-spectrum small-molecule and antibody direct-acting antivirals, but also on host-factor therapeutics, including repurposing previously approved or in-pipeline drugs. Another new class of therapeutics with great antiviral therapeutic potential is RNA-based therapeutics. Rather than only focusing on known risks, dedicated efforts must be made toward pre-emptive research focused on outbreak-prone virus families, ultimately offering a strategy to shorten the gap between outbreak and response. Emphasis should also focus on orally available drugs for outpatient use, if possible, and on identifying combination therapies that combat viral and immune-mediated pathologies, extend the effectiveness of therapeutic windows and reduce drug resistance. While such an undertaking will require new vision, dedicated funding and private, federal and academic partnerships, this approach offers hope that global populations need never experience future pandemics such as COVID-19.

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Section: Development Of Critical Tools and Methodsmentioning

confidence: 99%

Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases

Meganck

Baric

2021

Nat Med

180

161

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“…TH membranes are extensively used in biomimetic systems. In these systems, the role of TH membranes is to create in‐vivo‐like tissue interfaces, such as the gut epithelium, [ 114 ] vasculature, [ 115,116 ] lung, [ 117,118 ] renal, [ 119,120 ] liver, [ 121 ] and others. [ 122–126 ] M‐PM can realize cell migration across the membrane and allow physical contact between the two cell populations that grow on either side of the membrane for signal communication.…”

Section: Application Of M/n‐pmsmentioning

confidence: 99%

“…Moreover, another human alveolar chip lately reported by Qin's group was demonstrated to be able to recapitulate lung injury and immune responses induced by Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in vitro at organ level. [ 118 ] A thin (≈25 µm) PDMS TH membrane (5 µm pores in diameter) coated with extracellular matrix was sandwiched between the upper and bottom channels of the chip to construct the tissue‐tissue interface. This chip reproduced the key features of alveolar‐capillary barrier by co‐culture of human alveolar epithelium, microvascular endothelium, and circulating immune cells under fluidic flow in while normal and when diseased.…”

Section: Application Of M/n‐pmsmentioning

confidence: 99%

Advances in Micro/Nanoporous Membranes for Biomedical Engineering

Sun

Han

et al. 2021

Adv Healthcare Materials

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Porous membrane materials at the micro/nanoscale have exhibited practical and potential value for extensive biological and medical applications associated with filtration and isolation, cell separation and sorting, micro‐arrangement, in‐vitro tissue reconstruction, high‐throughput manipulation and analysis, and real‐time sensing. Herein, an overview of technological development of micro/nanoporous membranes (M/N‐PMs) is provided. Various membrane types and the progress documented in membrane fabrication techniques, including the electrochemical‐etching, laser‐based technology, microcontact printing, electron beam lithography, imprinting, capillary force lithography, spin coating, and microfluidic molding are described. Their key features, achievements, and limitations associated with micro/nanoporous membrane (M/N‐PM) preparation are discussed. The recently popularized applications of M/N‐PMs in biomedical engineering involving the separation of cells and biomolecules, bioparticle operations, biomimicking, micropatterning, bioassay, and biosensing are explored too. Finally, the challenges that need to be overcome for M/N‐PM fabrication and future applications are highlighted.

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“…By administering previously approved drugs in the airway chips under flow at a clinically relevant dose prior to infection, amodiaquine and toremifene were identified as potential entry inhibitors for SARS-CoV-2 [59]. Another recent work was reported by Zhang et al who described a biomimetic human disease model of SARS-CoV-2 infection, recapitulating lung injury and immune responses induced by the virus on chip, hence providing a unique platform that closely mirrored human-relevant responses to SARS-CoV-2 infection [60]. These pioneering studies have unlocked a new step for the use of airway chips to accelerate drug discovery and drug repurposing during viral pandemics.…”

Section: Virusesmentioning

confidence: 99%

Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin

Baddal

Marrazzo

2021

Pathogens

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Bioinspired organ-level in vitro platforms that recapitulate human organ physiology and organ-specific responses have emerged as effective technologies for infectious disease research, drug discovery, and personalized medicine. A major challenge in tissue engineering for infectious diseases has been the reconstruction of the dynamic 3D microenvironment reflecting the architectural and functional complexity of the human body in order to more accurately model the initiation and progression of host–microbe interactions. By bridging the gap between in vitro experimental models and human pathophysiology and providing alternatives for animal models, organ-on-chip microfluidic devices have so far been implemented in multiple research areas, contributing to major advances in the field. Given the emergence of the recent pandemic, plug-and-play organ chips may hold the key for tackling an unmet clinical need in the development of effective therapeutic strategies. In this review, latest studies harnessing organ-on-chip platforms to unravel host–pathogen interactions are presented to highlight the prospects for the microfluidic technology in infectious diseases research.

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Biomimetic Human Disease Model of SARS‐CoV‐2‐Induced Lung Injury and Immune Responses on Organ Chip System

Cited by 149 publications

References 54 publications

Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases

Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases

Advances in Micro/Nanoporous Membranes for Biomedical Engineering

Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin

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