Development of digital organ-on-a-chip to assess hepatotoxicity and extracellular vesicle-based anti-liver cancer immunotherapy

Wu, Guohua; Wu, Jianguo; Shi, Shengyu; Wu, Di; Wang, Xuanbo; Han, Xu; Liu, Hui; Huang, Yixiao; Wang, Rending; Shen, Jia; Dong, Zhihong; Wang, Shuqi

doi:10.1007/s42242-022-00188-1

Cited by 16 publications

(12 citation statements)

References 59 publications

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“…Even at the stage of preclinical evaluation, it is critical to select and develop a proper animal model that will also meet economic sustainability. But in this instance, organ-on-a-chip can be a powerful, robust tool to look further into the mechanism of action of the exosome, its ability for drug delivery, and assess its potency (Wu et al 2022 ). Exosomes are not bounded to animals but plants and plant parts, fruit juices have been found to be a potential origin (Yang et al 2020 b; Bruno et al 2021 ).…”

Section: Current Scenario and Future Prospect Of Exosomesmentioning

confidence: 99%

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives

et al. 2023

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Exosomes are nanosized (size ~ 30–150 nm) natural vesicular structures released from cells by physiological processes or pathological circumstances. Exosomes are growing in popularity as a result of their many benefits over conventional nanovehicles, including their ability to escape homing in the liver or metabolic destruction and their lack of undesired accumulation before reaching their intended targets. Various therapeutic molecules, including nucleic acids, have been incorporated into exosomes by different techniques, many of which have shown satisfactory performance in various diseases. Surface-modified exosomes are a potentially effective strategy, and it increases the circulation time and produces the specific drug target vehicle. In this comprehensive review, we describe composition exosomes biogenesis and the role of exosomes in intercellular signaling and cell–cell communications, immune responses, cellular homeostasis, autophagy, and infectious diseases. In addition, we discuss the role of exosomes as diagnostic markers, and their therapeutic and clinical implications. Furthermore, we addressed the challenges and outstanding developments in exosome research and discuss future perspectives. In addition to the current status of exosomes as a therapeutic carrier, the lacuna in the clinical development lifecycles along with the possible strategies to fill the lacuna have been addressed.

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Section: Current Scenario and Future Prospect Of Exosomesmentioning

confidence: 99%

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives

et al. 2023

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“…352 The digital organ-on-a-chip platform provides highparallelism and a low-variability analytical tool for toxicity assessment to combat cancer. 353 High-tech technologies such as biofabrication, artificial intelligence (AI), robotics, and automation benefits the OoC technology regularly. 354 Edington et al defined the interconnected microphysiological systems for quantitative biology and pharmacology studies.…”

Section: Trending Research Focused Technology and Limitationsmentioning

confidence: 99%

“…Digital technology such as deep learning for image digitization, data analysis, and automation contribute in OoC extensively . The digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment to combat cancer . High-tech technologies such as biofabrication, artificial intelligence (AI), robotics, and automation benefits the OoC technology regularly .…”

Section: Trending Research Focused Technology and Limitationsmentioning

confidence: 99%

Advances in Organ-on-a-Chip Materials and Devices

Nahak¹,

Mishra²,

Preetam³

et al. 2022

ACS Appl. Bio Mater.

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The organ-on-a-chip (OoC) paves a way for biomedical applications ranging from preclinical to clinical translational precision. The current trends in the in vitro modeling is to reduce the complexity of human organ anatomy to the fundamental cellular microanatomy as an alternative of recreating the entire cell milieu that allows systematic analysis of medicinal absorption of compounds, metabolism, and mechanistic investigation. The OoC devices accurately represent human physiology in vitro; however, it is vital to choose the correct chip materials. The potential chip materials include inorganic, elastomeric, thermoplastic, natural, and hybrid materials. Despite the fact that polydimethylsiloxane is the most commonly utilized polymer for OoC and microphysiological systems, substitute materials have been continuously developed for its advanced applications. The evaluation of human physiological status can help to demonstrate using noninvasive OoC materials in real-time procedures. Therefore, this Review examines the materials used for fabricating OoC devices, the application-oriented pros and cons, possessions for device fabrication and biocompatibility, as well as their potential for downstream biochemical surface alteration and commercialization. The convergence of emerging approaches, such as advanced materials, artificial intelligence, machine learning, three-dimensional (3D) bioprinting, and genomics, have the potential to perform OoC technology at next generation. Thus, OoC technologies provide easy and precise methodologies in cost-effective clinical monitoring and treatment using standardized protocols, at even personalized levels. Because of the inherent utilization of the integrated materials, employing the OoC with biomedical approaches will be a promising methodology in the healthcare industry.

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“…Although these previous studies were applied to recapitulate the disease, the effect of gut microbiome-derived metabolites and extracellular vesicles (EVs) have rarely been investigated. To date, only a few studies have investigated an organ-on-a-chip to explore the microbiome-derived metabolites and EVs [8][9][10]. Therefore, there is a need to understand how such metabolites or EVs can affect cellular functions at in vivo-like microenvironments.…”

Section: Introductionmentioning

confidence: 99%

Effect of gut microbiome-derived metabolites and extracellular vesicles on hepatocyte functions in a gut-liver axis chip

Kang

Choi

Mo³

et al. 2023

Nano Convergence

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Metabolism, is a complex process involving the gut and the liver tissue, is difficult to be reproduced in vitro with conventional single cell culture systems. To tackle this challenge, we developed a gut-liver-axis chip consisting of the gut epithelial cell chamber and three-dimensional (3D) uniform-sized liver spheroid chamber. Two cell culture chamber compartments were separated with a porous membrane to prevent microorganisms from passing through the chamber. When the hepG2 spheroids cultured with microbiota-derived metabolites, we observed the changes in the physiological function of hepG2 spheroids, showing that the albumin and urea secretion activity of liver spheroids was significantly enhanced. Additionally, the functional validation of hepG2 spheroids treated with microbiota-derived exosome was evaluated that the treatment of the microbiota-derived exosome significantly enhanced albumin and urea in hepG2 spheroids in a gut-liver axis chip. Therefore, this gut-liver axis chip could be a potentially powerful co-culture platform to study the interaction of microbiota and host cells. Graphical Abstract

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Development of digital organ-on-a-chip to assess hepatotoxicity and extracellular vesicle-based anti-liver cancer immunotherapy

Cited by 16 publications

References 59 publications

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives

Advances in Organ-on-a-Chip Materials and Devices

Effect of gut microbiome-derived metabolites and extracellular vesicles on hepatocyte functions in a gut-liver axis chip

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