Agarose microgel culture delineates lumenogenesis in naive and primed human pluripotent stem cells

Schindler, Magdalena; Siriwardena, Dylan; Kohler, Timo N.; Ellermann, Anna Lena; Slatery, Erin; Munger, Clara; Hollfelder, Florian; Boroviak, Thorsten

doi:10.1016/j.stemcr.2021.04.009

Cited by 21 publications

(10 citation statements)

References 69 publications

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“…This rosette-like structure consisting of Huh7 + PI3Kδ cells, surrounded by a dense ECM visible by laminin-111 labeling (Fig. 2a ), is reminiscent of not only liver progenitor cells/small cholangiocytes 23 but also stem cells that polarize during embryonic development 24 and stem cells grown in 3D in Matrigel 25 – 27 . Thus, we analyzed the expression of epithelial surface protein (EpCAM) (Fig.…”

Section: Resultsmentioning

confidence: 99%

PI3Kδ activity controls plasticity and discriminates between EMT and stemness based on distinct TGFβ signaling

et al. 2022

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The stem cells involved in formation of the complex human body are epithelial cells that undergo apicobasal polarization and form a hollow lumen. Epithelial plasticity manifests as epithelial to mesenchymal transition (EMT), a process by which epithelial cells switch their polarity and epithelial features to adopt a mesenchymal phenotype. The connection between the EMT program and acquisition of stemness is now supported by a substantial number of reports, although what discriminates these two processes remains largely elusive. In this study, based on 3D organoid culture of hepatocellular carcinoma (HCC)-derived cell lines and AAV8-based protein overexpression in the mouse liver, we show that activity modulation of isoform δ of phosphoinositide 3-kinase (PI3Kδ) controls differentiation and discriminates between stemness and EMT by regulating the transforming growth factor β (TGFβ) signaling. This study provides an important tool to control epithelial cell fate and represents a step forward in understanding the development of aggressive carcinoma.

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Section: Resultsmentioning

confidence: 99%

PI3Kδ activity controls plasticity and discriminates between EMT and stemness based on distinct TGFβ signaling

et al. 2022

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“…[205] Agarose can be cross-linked with decreasing temperature, with the phase-transition temperatures depending on different derivates. [206,207] It has been widely used in electrophoresis, protein purification and immunodiffusion, bacterial culture, and 3D culture of human and animal cells. [208][209][210] As a result of the biocompatibility, potential to be modified, reversible thermoinduced gelation, and tunable mechanical properties, agarose is a promising material for the development of microgels.…”

Section: Diversity In Materials For Microgelsmentioning

confidence: 99%

Recent Advances in Microgels: From Biomolecules to Functionality

Zhu

Denduluri

et al. 2022

Small

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The emerging applications of hydrogel materials at different length scales, in areas ranging from sustainability to health, have driven the progress in the design and manufacturing of microgels. Microgels can provide miniaturized, monodisperse, and regulatable compartments, which can be spatially separated or interconnected. These microscopic materials provide novel opportunities for generating biomimetic cell culture environments and are thus key to the advances of modern biomedical research. The evolution of the physical and chemical properties has, furthermore, highlighted the potentials of microgels in the context of materials science and bioengineering. This review describes the recent research progress in the fabrication, characterization, and applications of microgels generated from biomolecular building blocks. A key enabling technology allowing the tailoring of the properties of microgels is their synthesis through microfluidic technologies, and this paper highlights recent advances in these areas and their impact on expanding the physicochemical parameter space accessible using microgels. This review finally discusses the emerging roles that microgels play in liquid–liquid phase separation, micromechanics, biosensors, and regenerative medicine.

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“…Cells inside the 'liquid marbles' freely interact with each other and aggregate as uniformed spheroids/organoids within 24 hours [62]. Using the microfluidic system, a cell-hydrogel mixture can be encapsulated into microgels, where the cells proliferate and condense into spheroids/organoids [63,64]. The spheroids-in-gel can also be formed from cell pellets within the solidified matrigel droplets on the plate bottom, within which cell cores grow into spheroid/organoid inside each droplet [65].…”

Section: Scaffold-based Culturesmentioning

confidence: 99%

Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models

Liu

Xu²,

Abraham³

et al. 2022

IJDDP

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Review Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models Yingjuan Liu *, Honglin Xu, Sabu Abraham, Xin Wang, and Bernard D. Keavney* Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK. * Correspondence: yingjuan.liu@manchester.ac.uk (Yingjuan Liu); bernard.keavney@manchester.ac.uk (Bernard D. Keavney) Received: 1 November 2022 Accepted: 24 November 2022 Published: 21 December 2022 Abstract: Currently, with an increased requirement for new therapeutic strategies, preclinical drug testing or screening platforms have rapidly evolved in recent years. In comparison to traditional 2D cell cultures, 3D organoids or spheroids with or without scaffolds improve the microenvironment of in vitro cultures, advancing the in vitro biological observation and enabling mechanistic studies of drug reactions in the human tissue-like environment. 3D organoids and spheroids are straightforward to produce, and relatively uniform in size and shape. This helps to facilitate high throughput screening requirements. Spheroids and organoids have been applied in anti-cancer drug testing, toxicity evaluations, as well as mechanism studies for variable organ systems, including the intestine, liver, pancreas, brain, and heart. Among 3D cultures of spheroids and organoids, ‘tumour spheroids’ formed by dissociated tumour tissues or cancer cell lines are relatively simple in composition and commonly applied to anticancer drug screening. The ‘healthy organoids’ differentiated from hiPSCs/hESCs are more complex in cell composition, distribution, structure and function with higher similarity to in vivo organs, and have found applications in toxicity tests, personalised medicine, and therapeutic and mechanistic studies. In most cases, the multicellular 3D organoids are more resistant and stable in reaction to stimulations or chemicals in vitro , suggesting more accurate modelling of in vivo responses. Here, we review recent progress in human-origin organoid/spheroid systems and their applications in preclinical studies.

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Agarose microgel culture delineates lumenogenesis in naive and primed human pluripotent stem cells

Cited by 21 publications

References 69 publications

PI3Kδ activity controls plasticity and discriminates between EMT and stemness based on distinct TGFβ signaling

PI3Kδ activity controls plasticity and discriminates between EMT and stemness based on distinct TGFβ signaling

Recent Advances in Microgels: From Biomolecules to Functionality

Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models

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