Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing

Lu, Shu‐Ling; Cuzzucoli, Fabio; Jiang, Jing; Liang, Liguo; Wang, Yimin; Kong, Mengqi; Zhao, Xin; Cui, Wenguo; Li, Jun; Wang, Shuqi

doi:10.1039/c8lc00852c

Cited by 121 publications

(94 citation statements)

References 37 publications

(37 reference statements)

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“…These systems can recapitulate the biochemical, mechanical, structural, and functional features of human organs by mimicking in vivo‐like cellular microenvironment . Researchers have engineered a variety of miniaturized models of human organs, such as liver, lung, intestine, kidney, and heart . These models can potentially bridge the gap between in vitro tests and clinical trials and be utilized for more precise drug prediction in pharmaceutical field in comparison to animal models.…”

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

“…Hydrogels acted as 3D matrices or scaffolds have been incorporated into OOC to engineer human tissues with multicellular architecture and organ‐specific functions by spatial control of microenvironment cues . A variety of 3D parenchymal tissues in hydrogel‐based organs‐on‐chips have been reported, such as liver, heart, skeletal muscle, intestine, and nasal mucosa …”

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

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Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…Microfluidic models of pancreatic ductal adenocarcinoma demonstrated transcriptome level similarity to patient-derived pancreatic stellate cells (Gioeli et al, 2019). To model liver metastasis, gelatin methacryloyl was combined with decellularized liver matrix components including bioactive factors derived from liver matrix, in a dynamic culture system to assess drug-dose responses to acetaminophen and sorafenib (Lu et al, 2018). In a similar metastasis-on-a-chip model of kidney cancer metastasized to the liver, NP-conjugated 5fluorouracil was shown to be more efficacious than free drug (Wang et al, 2020).…”

Section: Microfluidic Organ-on-a-chipmentioning

confidence: 99%

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

Frieboes

Raghavan

Godin

2020

Front. Bioeng. Biotechnol.

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The tumor microenvironment (TME) presents a challenging barrier for effective nanotherapy-mediated drug delivery to solid tumors. In particular for tumors less vascularized than the surrounding normal tissue, as in liver metastases, the structure of the organ itself conjures with cancer-specific behavior to impair drug transport and uptake by cancer cells. Cells and elements in the TME of hypovascularized tumors play a key role in the process of delivery and retention of anti-cancer therapeutics by nanocarriers. This brief review describes the drug transport challenges and how they are being addressed with advanced in vitro 3D tissue models as well as with in silico mathematical modeling. This modeling complements network-oriented techniques, which seek to interpret intra-cellular relevant pathways and signal transduction within cells and with their surrounding microenvironment. With a concerted effort integrating experimental observations with computational analyses spanning from the molecular-to the tissue-scale, the goal of effective nanotherapy customized to patient tumor-specific conditions may be finally realized.

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“…Hydrogel precursors are injected into a microfluidic device using a pipette and photopolymerized by UV exposure to form HepG2-laden DLM-GelMA for subsequent drug screening. Reproduced with permission from[71].…”

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confidence: 99%

Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

et al. 2019

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Hepatology and drug development for liver diseases require in vitro liver models. Typical models include 2D planar primary hepatocytes, hepatocyte spheroids, hepatocyte organoids, and liver-on-a-chip. Liver-on-a-chip has emerged as the mainstream model for drug development because it recapitulates the liver microenvironment and has good assay robustness such as reproducibility. Liver-on-a-chip with human primary cells can potentially correlate clinical testing. Liver-on-a-chip can not only predict drug hepatotoxicity and drug metabolism, but also connect other artificial organs on the chip for a human-on-a-chip, which can reflect the overall effect of a drug. Engineering an effective liver-on-a-chip device requires knowledge of multiple disciplines including chemistry, fluidic mechanics, cell biology, electrics, and optics. This review first introduces the physiological microenvironments in the liver, especially the cell composition and its specialized roles, and then summarizes the strategies to build a liver-on-a-chip via microfluidic technologies and its biomedical applications. In addition, the latest advancements of liver-on-a-chip technologies are discussed, which serve as a basis for further liver-on-a-chip research.

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Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing

Abstract: A tumor-on-a-chip platform with integration of decellularized liver matrix offers better biomimicry of tumor microenvironment and enhanced toxicity testing.

Cited by 121 publications

References 37 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

Engineered Liver-On-A-Chip Platform to Mimic Liver Functions and Its Biomedical Applications: A Review

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