Hepatic spheroids used as an in vitro model to study malaria relapse

Chua, Adeline C. Y.; Ananthanarayanan, Abhishek; Ong, Jessica Jie Ying; Wong, Jen Yi; Yip, Andy M.; Singh, Nisha Hari; Qu, Yinghua; Dembélé, Laurent; McMillian, Michael; Ubalee, Ratawan; Davidson, Silas A.; Tungtaeng, Anchalee; Im-Erbsin, Rawiwan; Gupta, Kapish; Andolina, Chiara; Lee, Fan; Tan, Kevin S. W.; Nosten, François; Russell, Bruce; Lange, Amber; Diagana, Thierry T.; Rénia, Laurent; Yeung, Bryan K. S.; Yu, Hanry; Bifani, Pablo

doi:10.1016/j.biomaterials.2019.05.032

Cited by 53 publications

(57 citation statements)

References 69 publications

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“…21 For our specific application, we determined the hepatocytes should be cultured in an adhered monolayer format, producing a relatively two-dimensional cell monolayer in each microfeature, to avoid spheroid formation as multi-cellular structures can be difficult to image and characterize in a single focal plane during high-content imaging. 25,26 Regarding material selection, previously described microwell systems have been fabricated from PEG hydrogel, 27 heparin hydrogel, 28 agarose, 22 PDMS, [29][30][31] or PS. 21,32 To maintain optical accessibility and take advantage of the bulk-material properties ideal for small molecule testing, 33 we fabricated systems from stock PS, and tested several surface treatments and coatings to encourage formation of a hepatic monolayer and promote stable, longterm culture.…”

Section: Introductionmentioning

confidence: 99%

An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing

et al. 2020

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Section: Introductionmentioning

confidence: 99%

An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing

et al. 2020

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“…It was found that P. yoelii and P. falciparum infections of organoids recapitulated the primaquine sensitivity found in vivo. Chua and colleagues (Chua et al 2019 ) infected organoids derived from simian and human hepatocytes, with P. cynomolgi and P. vivax and found that organoids could support the complete liver stage of both simian and human parasites, from initial infection with sporozoites, to the release of merozoites capable of erythrocyte infection. This study also illustrated the use of infected organoids to evaluate the response to an anti-relapse drug, highlighting the potential for organoids as a parasite drug screening platform, particularly in parasites with life-cycles longer than their host cells.…”

Section: Organoids For Basic Researchmentioning

confidence: 99%

Organoid based personalized medicine: from bench to bedside

Tang

Cai

et al. 2020

Cell Regen

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Three-dimensional cultured organoids have become a powerful in vitro research tool that preserves genetic, phenotypic and behavioral trait of in vivo organs, which can be established from both pluripotent stem cells and adult stem cells. Organoids derived from adult stem cells can be established directly from diseased epithelium and matched normal tissues, and organoids can also be genetically manipulated by CRISPR-Cas9 technology. Applications of organoids in basic research involve the modeling of human development and diseases, including genetic, infectious and malignant diseases. Importantly, accumulating evidence suggests that biobanks of patient-derived organoids for many cancers and cystic fibrosis have great value for drug development and personalized medicine. In addition, organoids hold promise for regenerative medicine. In the present review, we discuss the applications of organoids in the basic and translational research.

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“…Cellulosic sponges have been used to culture human and simian primary hepatocyte spheroids, and the long-term cell viability and hepatic characteristics permitted malaria parasites to fully develop from sporozoites. [138] These hepatocyte spheroids also provided a platform to screen drugs for malaria treatment. HLCs derived from specific patients' iPSCs are a powerful tool in large-scale genomic studies [139] and in investigating molecular pathways of genetic diseases such as Figure 5.…”

Section: Disease Modeling and Diagnosismentioning

confidence: 99%

Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine

Huang

Gibeley

et al. 2020

Adv Funct Materials

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The burden of liver diseases is increasing worldwide, accounting for two million deaths annually. In the past decade, tremendous progress has been made in the basic and translational research of liver tissue engineering. Liver microtissues are small, 3D hepatocyte cultures that recapitulate liver physiology and have been used in biomedical research and regenerative medicine. This review summarizes the recent advances, challenges, and future directions in liver microtissue research. Cellular engineering approaches are used to sustain primary hepatocytes or produce hepatocytes derived from pluripotent stem cells and other adult tissues. 3D microtissues are generated using scaffoldfree assembly or scaffold-assisted methods such as macroencapsulation, droplet microfluidics, and bioprinting. Optimization of the hepatic microenvironment entails incorporating the appropriate cell composition for enhanced cell-cell interactions and niche-specific signals, and creating scaffolds with desired chemical, mechanical, and physical properties. Perfusion-based culture systems such as bioreactors and microfluidic systems are used to achieve efficient exchange of nutrients and soluble factors. Taken together, systematic optimization of liver microtissues is a multidisciplinary effort focused on creating liver cultures and on-chip models with greater structural complexity and physiological relevance for use in liver disease research, therapeutic development, and regenerative medicine.

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Hepatic spheroids used as an in vitro model to study malaria relapse

Cited by 53 publications

References 69 publications

An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing

An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing

Organoid based personalized medicine: from bench to bedside

Engineering Liver Microtissues for Disease Modeling and Regenerative Medicine

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