Multicellular Liver Organoids: Generation and Importance of Diverse Specialized Cellular Components (2024)

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Frontiers in Medicine

Liver Organoids: Recent Developments, Limitations and Potential

2021 •

gareth sullivan

Liver cell types derived from induced pluripotent stem cells (iPSCs) share the potential to investigate development, toxicity, as well as genetic and infectious disease in ways currently limited by the availability of primary tissue. With the added advantage of patient specificity, which can play a role in all of these areas. Many iPSC differentiation protocols focus on 3 dimensional (3D) or organotypic differentiation, as these offer the advantage of more closely mimicking in vivo systems including; the formation of tissue like architecture and interactions/crosstalk between different cell types. Ultimately such models have the potential to be used clinically and either with or more aptly, in place of animal models. Along with the development of organotypic and micro-tissue models, there will be a need to co-develop imaging technologies to enable their visualization. A variety of liver models termed “organoids” have been reported in the literature ranging from simple spheres or cys...

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Hepatology (Baltimore, Md.)

Self-assembled liver organoids recapitulate hepato-biliary organogenesis in vitro

2017 •

Brandon Gaston

Several 3D cell culture systems are currently available to create liver organoids. In general, these systems display better physiologic and metabolic aspects of intact liver tissue, compared with 2D culture systems. However, none of these reliably mimic human liver development, including parallel formation of hepatocyte and cholangiocyte anatomical structures. Here, we show that human fetal liver progenitor cells self-assemble inside acellular liver extracellular matrix (ECM) scaffolds to form 3D liver organoids that recapitulated several aspects of hepato-biliary organogenesis and resulted in concomitant formation of progressively more differentiated hepatocytes and bile duct structures. The duct morphogenesis process was interrupted by inhibiting Notch signaling, attempting to create a liver developmental disease model with a similar phenotype of Alagille syndrome. In the current study, we created an in vitro model of human liver development and disease, physiology and metabolism,...

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International Journal of Molecular Sciences

Liver Organoids as an In Vitro Model to Study Primary Liver Cancer

Cristian Turato

Primary liver cancers (PLC), including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are among the leading causes of cancer-related mortality worldwide. Bi-dimensional in vitro models are unable to recapitulate the key features of PLC; consequently, recent advancements in three-dimensional in vitro systems, such as organoids, opened up new avenues for the development of innovative models for studying tumour’s pathological mechanisms. Liver organoids show self-assembly and self-renewal capabilities, retaining essential aspects of their respective in vivo tissue and allowing modelling diseases and personalized treatment development. In this review, we will discuss the current advances in the field of liver organoids focusing on existing development protocols and possible applications in regenerative medicine and drug discovery.

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In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells

2015 •

Katja Breitkopf-Heinlein

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Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids

2018 •

Onur Basak

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Liver sinusoidal endothelial cells promote the differentiation and survival of mouse vascularised hepatobiliary organoids

2020 •

George Yeoh

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Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment

2019 •

Monique Verstegen

Primary liver cancer, consisting predominantly of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), remains one of the most lethal malignancies worldwide. This high malignancy is related to the complex and dynamic interactions between tumour cells, stromal cells and the extracellular environment. Novel in vitro models that can recapitulate the tumour are essential in increasing our understanding of liver cancer. Herein, primary liver cancer-derived organoids have opened up new avenues due to their patient-specificity, self-organizing ability and potential recapitulation of many of the tumour properties. Organoids are solely of epithelial origin, but incorporation into co-culture models can enable the investigation of the cellular component of the tumour microenvironment. However, the extracellular component also plays a vital role in cancer progression and representation is lacking within current in vitro models. In this review, organoid technology is discussed in the con...

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Modeling liver cancer and therapy responsiveness using organoids derived from primary mouse liver tumors

2018 •

Maikel Peppelenbosch

The current understanding of cancer biology and development of effective treatments for cancer remain far from satisfactory. This in turn heavily relies on the availability of easy and robust model systems that resemble the architecture/physiology of the tumors in patients to facilitate research. Cancer research in vitro has mainly been based on the use of immortalized 2D cancer cell lines that deviate in many aspects from the original primary tumors. The recent development of the organoid technology allowing generation of organ-buds in 3D culture from adult stem cells has endowed the possibility of establishing stable culture from primary tumors. Although culturing organoids from liver tumors is thought to be difficult, we now convincingly demonstrate the establishment of organoids from mouse primary liver tumors. We have succeeded in culturing 91 lines from 129 liver tissue/tumors. These organoids can be grown in long-term cultures in vitro. About 20% of these organoids form tumor...

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Stem Cell Reports

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

2019 •


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The American Journal of Pathology

Histological Organization in Hepatocyte Organoid Cultures

2001 •

George Michalopoulos

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Multicellular Liver Organoids: Generation and Importance of Diverse Specialized Cellular Components (2024)
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