Liver Organoids: Updates on Disease Modeling and Biomedical Applications

Caiazza, Carmen; Parisi, Silvia; Caiazzo, Massimiliano

doi:10.3390/biology10090835

Cited by 17 publications

(15 citation statements)

References 60 publications

(84 reference statements)

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“…Unlike patient-derived liver and intestine organoids, brain organoids have not been cryopreserved, thawed, and re-cultured, an aspect that limits the flexible and economical use of brain organoids 28, 29 . We could successfully freeze 8-day-old Hi-Q brain organoids, cryopreserved them in liquid nitrogen for four days and re-cultured them after thawing (Figure 5A, see method section).…”

Section: Resultsmentioning

confidence: 99%

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion, and drug screening

Ramani,

Pasquini,

Gerkau

et al. 2023

Preprint

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SUMMARYBrain organoids offer unprecedented insights into brain development and disease modeling and hold promise for drug screening. Significant hindrances, however, are morphological and cellular heterogeneity, inter-organoid size differences, cellular stress, and poor reproducibility. Here, we describe a method that reproducibly generates thousands of organoids across multiple iPSC lines. These High Quantity brain organoids (Hi-Q brain organoids) exhibit reproducible cytoarchitecture, cell diversity, and functionality, are free from ectopically active cellular stress pathways, and allow cryopreservation and re-culturing. Using patient-derived Hi-Q brain organoids, we recapitulated distinct forms of microcephaly pathogenesis: primary microcephaly due to a mutation in centrosomal CDK5RAP2 and progeria-associated microcephaly in Cockayne syndrome. When modeling glioma invasion, hi-Q brain organoids displayed a similar invasion pattern for a given patient-derived glioma cell line. This enabled a medium-throughput screen to identify Selumetinib and Fulvestrant, which also perturbed glioma invasion in vivo. Thus, the Hi-Q approach can easily be adapted to reliably harness brain organoids’ utility for personalized disease modeling and drug discovery.

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Section: Resultsmentioning

confidence: 99%

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion, and drug screening

Ramani,

Pasquini,

Gerkau

et al. 2023

Preprint

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“…This includes the development of reproducible methods for the composition and functionality of organoids and the enhancement of cellular maturation to ensure greater resemblance to pathophysiological processes. However, the results obtained to date are promising and represent a potential paradigm shift in the management of acute and chronic liver and biliary diseases [ 146 ].…”

Section: Discussionmentioning

confidence: 99%

Cholangiocyte Organoids: The New Frontier in Regenerative Medicine for the Study and Treatment of Cholangiopathies

Babboni,

Vacca,

Simonini

et al. 2024

JCM

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Cholangiopathies include a group of chronic progressive disorders, affecting the cholangiocytes, the epithelial cells that line the biliary tree, leading to liver parenchymal fibrosis and eventually end-stage liver disease necessitating transplantation. Experimental modeling of these multifactorial cholestatic diseases faces challenges due to the lack of adequate experimental in vitro and in vivo models. A novel approach employs three-dimensional organoid systems that offer several advantages for modeling disease and testing drug response in vitro. Organoids mimic intercellular communication, replicate the architecture of organs, and maintain the cell’s original phenotype. Cholangiocyte organoids provide an in vitro model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies and show great promise for regenerative therapies. In particular, patient-derived organoids allow personalized medicine approaches and the study of individual disease characteristics. This review highlights the significance of cholangiocyte organoid models in advancing our understanding of cholangiopathies and driving advancements in regenerative medicine strategies.

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“…Organoids derived from diseased tissues recapitulate the genomic background of individual patients and retain the functional dysregulations in monogenetic disorders. 29,[47][48][49] In addition, genome editing technology enables the precise insertion and correction of mutated sequences for further mechanistic study. Clevers's group reported the first platform for isolating bipotent intrahepatic cholangiocyte organoids (ICO) from healthy and diseased tissues.…”

Section: Hereditary Liver Diseasementioning

confidence: 99%

A decade of liver organoids: Advances in disease modeling

Liu¹,

Sheng²,

Ding³

et al. 2023

Clin Mol Hepatol

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Liver organoids are 3D cellular models of tissue in which cells interact to form unique structures in culture. Since their inception, liver organoids with various cellular compositions, structural features, and functional properties have been described over the past ten years. Methods to create these advanced human cell models range from simple tissue culture techniques to complex bioengineering approaches. These liver organoid culture platforms have been utilized in various liver research fields, including the modeling of liver diseases to regenerative therapy. This review will discuss how liver organoids are used to model diseases, including hereditary liver diseases, primary liver cancer, viral hepatitis, and nonalcoholic fatty liver disease. Specifically, we will focus on studies that utilized two widely adopted approaches: differentiation from pluripotent stem cells and epithelial organoids cultured from patient tissues. These approaches have enabled the generation of advanced human liver models and, more importantly, the establishment of patient-tailored models for evaluating individual-specific disease phenotypes and therapeutic responses.

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Liver Organoids: Updates on Disease Modeling and Biomedical Applications

Cited by 17 publications

References 60 publications

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion, and drug screening

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion, and drug screening

Cholangiocyte Organoids: The New Frontier in Regenerative Medicine for the Study and Treatment of Cholangiopathies

A decade of liver organoids: Advances in disease modeling

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