<i>In situ</i> differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system

Wang, Yaqing; Wang, Hui; Deng, Pengwei; Chen, Wenwen; Guo, Yaqiong; Tao, Tingting; Qin, Jianhua

doi:10.1039/c8lc00869h

Cited by 167 publications

(142 citation statements)

References 39 publications

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“…This strategy can be applied to other microfluidic organ models, which provides an opportunity to query patient-specific liver responses in vitro. Another hiPSC-induced liver organoid-on-a-chip system also demonstrated a promising organoid-based liver chip platform with applications in precision medicine and disease modeling [107].…”

Section: Establishment Of Liver Disease Modelsmentioning

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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Section: Establishment Of Liver Disease Modelsmentioning

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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“…Accordingly, organ-on-a-chip is also a valuable platform for drug development and toxicology giving insights into adsorption, distribution, metabolism, elimination, and toxicity (ADMET), mathematical pharmacokinetics (PK), pharmacodynamics (PD), and drug efficacy [134]. In fact, Wang and colleagues have recently achieved the in situ differentiation of hPSCs into liver organoids using a perfusable micropillar chip [135]. The on-chip liver organoids displayed both hepatocytes and cholangiocytes, as well as increased cell viability and mature cell signature.…”

Section: Drug Discovery and Hepatotoxicitymentioning

confidence: 99%

Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications

Cotovio

Fernandes

2020

Bioengineering

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Liver disease is one of the leading causes of death worldwide, leading to the death of approximately 2 million people per year. Current therapies include orthotopic liver transplantation, however, donor organ shortage remains a great challenge. In addition, the development of novel therapeutics has been limited due to the lack of in vitro models that mimic in vivo liver physiology. Accordingly, hepatic cell lineages derived from human pluripotent stem cells (hPSCs) represent a promising cell source for liver cell therapy, disease modelling, and drug discovery. Moreover, the development of new culture systems bringing together the multiple liver-specific hepatic cell types triggered the development of hPSC-derived liver organoids. Therefore, these human liver-based platforms hold great potential for clinical applications. In this review, the production of the different hepatic cell lineages from hPSCs, including hepatocytes, as well as the emerging strategies to generate hPSC-derived liver organoids will be assessed, while current biomedical applications will be highlighted.

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“…Liver buds were formed by self-organisation and cell-to-cell contact combined with paracrine signalling, resulting in induction of hepatic genes and expression of bile salt export pumps [97]. More recently, generation of liver organoids on a 3D perfusable chip has been reported [98]. These organoids had higher cell viability and expressed endodermal and mature hepatic genes.…”

Section: Liver Idosmentioning

confidence: 99%

Engineering Prostate Cancer from Induced Pluripotent Stem Cells—New Opportunities to Develop Preclinical Tools in Prostate and Prostate Cancer Studies

Hepburn

Sims

Buskin

et al. 2020

IJMS

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One of the key issues hampering the development of effective treatments for prostate cancer is the lack of suitable, tractable, and patient-specific in vitro models that accurately recapitulate this disease. In this review, we address the challenges of using primary cultures and patient-derived xenografts to study prostate cancer. We describe emerging approaches using primary prostate epithelial cells and prostate organoids and their genetic manipulation for disease modelling. Furthermore, the use of human prostate-derived induced pluripotent stem cells (iPSCs) is highlighted as a promising complimentary approach. Finally, we discuss the manipulation of iPSCs to generate ‘avatars’ for drug disease testing. Specifically, we describe how a conceptual advance through the creation of living biobanks of “genetically engineered cancers” that contain patient-specific driver mutations hold promise for personalised medicine.

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In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system

Abstract: We present a new strategy to engineer human iPSC-derived liver organoids by combining stem cell biology with a microfluidic chip system.

Cited by 167 publications

References 39 publications

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

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

Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications

Engineering Prostate Cancer from Induced Pluripotent Stem Cells—New Opportunities to Develop Preclinical Tools in Prostate and Prostate Cancer Studies

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