Human organoids: New strategies and methods for analyzing human development and disease

Corsini, Nina S.; Knoblich, Juergen A.

doi:10.1016/j.cell.2022.06.051

Cited by 64 publications

(48 citation statements)

References 115 publications

(190 reference statements)

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“…Disease modelling with 3D human organoids has the potential to bridge the gap between conventional animal models and humans. Organoids have been developed for numerous organ systems (reviewed in detail elsewhere 90 , 91 ) and are generally derived from pluripotent stem cells (PSCs), although some non-brain organoids can be generated from adult stem cells or fetus-derived cultures 92 , 93 . With respect to brain organoids, Sasai’s group pioneered the 3D in vitro culture of optic cup structures 94 , 95 and cortical tissue 96 , and our group developed the cerebral organoid model and pioneered its use for disease modelling 37 .…”

Section: Brain Organoids For Modellingmentioning

confidence: 99%

Human cerebral organoids — a new tool for clinical neurology research

2022

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The current understanding of neurological diseases is derived mostly from direct analysis of patients and from animal models of disease. However, most patient studies do not capture the earliest stages of disease development and offer limited opportunities for experimental intervention, so rarely yield complete mechanistic insights. The use of animal models relies on evolutionary conservation of pathways involved in disease and is limited by an inability to recreate human-specific processes. In vitro models that are derived from human pluripotent stem cells cultured in 3D have emerged as a new model system that could bridge the gap between patient studies and animal models. In this Review, we summarize how such organoid models can complement classical approaches to accelerate neurological research. We describe our current understanding of neurodevelopment and how this process differs between humans and other animals, making human-derived models of disease essential. We discuss different methodologies for producing organoids and how organoids can be and have been used to model neurological disorders, including microcephaly, Zika virus infection, Alzheimer disease and other neurodegenerative disorders, and neurodevelopmental diseases, such as Timothy syndrome, Angelman syndrome and tuberous sclerosis. We also discuss the current limitations of organoid models and outline how organoids can be used to revolutionize research into the human brain and neurological diseases.

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Section: Brain Organoids For Modellingmentioning

confidence: 99%

Human cerebral organoids — a new tool for clinical neurology research

2022

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“…A key concern of any screen or cell line/rodent-based studies for a human therapeutic agent, is that the experimental model will reveal highly selective promoters or capsids, but these only operate in that specific model due to its unusual biologyand may have limited utility across species. The advent of primary human cancer models provides a timely experimental advance that can help address these limitations 81 . These patient-derived cancer models can provide improved in vivo models when orthotopically transplanted into mouse tissues (immunocompromised mice).…”

Section: The Importance Of Patient-derived Tumour Modelsmentioning

confidence: 99%

“…The advent of primary human cancer models provides a timely experimental advance that can help address these limitations. 81 These patient-derived cancer models can provide improved in vivo models when orthotopically transplanted into mouse tissues (immunocompromised mice). These xenografts have more realistic histology and virus activity can therefore be explored through different delivery routes.…”

Section: The Importance Of Patient-derived Tumor Modelsmentioning

confidence: 99%

Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?

2022

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“…Key features of neuroepithelium generation, morphogenesis, and differentiation can be recapitulated with brain organoids, three-dimensional models of developing human brain regions ( Eichmüller & Knoblich , 2022; Pasca , 2018; Quadrato & Arlotta , 2017; Sidhaye & Knoblich , 2021). In vitro systems of various epithelial tissues are able to model aspects of endogenous morphogenesis with remarkable accuracy, but often lack endogenous ECM production, therefore requiring exogenous ECM supplementation ( Corsini & Knoblich , 2022; Inman & Bissell , 2010; Kratochvil et al ., 2019; Simian & Bissell , 2017). Accordingly, the vast majority of protocols used for brain organoid generation resorts to the early exposure of embryoid bodies (EBs) to exogenous ECM, which has been proposed as an adjuvant to the process of neuroepithelialisation ( Bhaduri et al ., 2020; Eichmüller et al ., 2022; Esk et al ., 2020; He et al ., 2022; Kelava et al ., 2022; Paulsen et al ., 2022; Qian et al ., 2018; Velasco et al ., 2019; Villa et al ., 2022).…”

Section: Introductionmentioning

confidence: 99%

Morphogenesis and development of human telencephalic organoids in the absence and presence of exogenous ECM

Martins‐Costa

Pham

Sidhaye

et al. 2022

Preprint

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Establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and the developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) is crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous ECM supplementation. While neuroepithelial development is recapitulated in cerebral organoids, the effects of different ECM sources in tissue morphogenesis remain unexplored. Here, we show that exposure to exogenous ECM at early neuroepithelial stages causes rapid tissue polarization and complete rearrangement of neuroepithelial architecture within 3 days. In unexposed cultures, endogenous ECM production by NPCs results in gradual polarity acquisition over an extended time. After the onset of neurogenesis, tissue architecture and neuronal differentiation are largely independent of the initial ECM source. These results advance the knowledge on neuroepithelial biology in vitro, with a focus on mechanisms of exogenously- and endogenously-guided morphogenesis. They demonstrate the self-sustainability of neuroepithelial cultures by endogenous processes, prompting an urgent reassessment of indiscriminate use of exogenous ECM in these model systems.

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Human organoids: New strategies and methods for analyzing human development and disease

Cited by 64 publications

References 115 publications

Human cerebral organoids — a new tool for clinical neurology research

Human cerebral organoids — a new tool for clinical neurology research

Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?

Morphogenesis and development of human telencephalic organoids in the absence and presence of exogenous ECM

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