Organoids for Drug Discovery and Personalized Medicine

Takahashi, Toshio

doi:10.1146/annurev-pharmtox-010818-021108

Cited by 155 publications

(133 citation statements)

References 134 publications

(117 reference statements)

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“…Currently organoids have been used to investigate gene function, cell development, tissue and cellular level physiology and model host-microbiome interactions. They are also useful for modelling infectious and genetic diseases, investigating primary tumour growth, and have applications in drug screening and regenerative medicine [20,21]. A further key driver of their utility, in addition to being a more physiologically relevant model, is their amenability to both standard and high-tech laboratory techniques and their genetic and molecular tractability.…”

Section: What Can Organoids Do For You?mentioning

confidence: 99%

Diabetes through a 3D lens: organoid models

2020

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Diabetes is one of the most challenging health concerns facing society. Available drugs treat the symptoms but there is no cure. This presents an urgent need to better understand human diabetes in order to develop improved treatments or target remission. New disease models need to be developed that more accurately describe the pathology of diabetes. Organoid technology provides an opportunity to fill this knowledge gap. Organoids are 3D structures, established from pluripotent stem cells or adult stem/progenitor cells, that recapitulate key aspects of the in vivo tissues they mimic. In this review we briefly introduce organoids and their benefits; we focus on organoids generated from tissues important for glucose homeostasis and tissues associated with diabetic complications. We hope this review serves as a touchstone to demonstrate how organoid technology extends the research toolbox and can deliver a step change of discovery in the field of diabetes.

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Section: What Can Organoids Do For You?mentioning

confidence: 99%

Diabetes through a 3D lens: organoid models

2020

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“…Self-organization is indeed the most important characteristic of organoids: Under opportune culture conditions (appropriate nutrients and growth factors) primary cells isolated from biopsies, embryonic or adult stem cells, and patient-derived iPSCs can go towards differentiation to develop a 'mini' organ according to intrinsic developmental patterns, thus generating a faithful replica of tissues' morphology and organization [142,143]. Therefore, organoids hold a great promise for ex vivo cell modeling as they are a powerful tool for developmental studies and personalized medicine [144]. Accordingly, organoids represent a major improvement in disease modeling compared to animal models, as they overcome ethical issues, are more cost-effective and allow faster analysis [144,145].…”

Section: Ex Vivo Stem Cell-based Systems: Organoidsmentioning

confidence: 99%

“…Therefore, organoids hold a great promise for ex vivo cell modeling as they are a powerful tool for developmental studies and personalized medicine [144]. Accordingly, organoids represent a major improvement in disease modeling compared to animal models, as they overcome ethical issues, are more cost-effective and allow faster analysis [144,145]. Since the development of the first intestinal organoids by Sato and collaborators in 2009 [146], many other models of various tissues have been developed following diverse approaches such as (i) Matrigel scaffold-based, (ii) Embryoid Bodies (EB)-based, and (iii) Air-Liquid Interface (ALI) method [147], and they have been used to model a great range of pathologies, from viral infection to solid cancers, cystic fibrosis, and endometriosis ( Table 5).…”

Section: Ex Vivo Stem Cell-based Systems: Organoidsmentioning

confidence: 99%

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

Argentati

Tortorella

Bazzucchi

et al. 2020

JPM

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Ex vivo cell/tissue-based models are an essential step in the workflow of pathophysiology studies, assay development, disease modeling, drug discovery, and development of personalized therapeutic strategies. For these purposes, both scientific and pharmaceutical research have adopted ex vivo stem cell models because of their better predictive power. As matter of a fact, the advancing in isolation and in vitro expansion protocols for culturing autologous human stem cells, and the standardization of methods for generating patient-derived induced pluripotent stem cells has made feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Furthermore, the potential of stem cells on generating more complex systems, such as scaffold-cell models, organoids, or organ-on-a-chip, allowed to overcome the limitations of the two-dimensional culture systems as well as to better mimic tissues structures and functions. Finally, the advent of genome-editing/gene therapy technologies had a great impact on the generation of more proficient stem cell-disease models and on establishing an effective therapeutic treatment. In this review, we discuss important breakthroughs of stem cell-based models highlighting current directions, advantages, and limitations and point out the need to combine experimental biology with computational tools able to describe complex biological systems and deliver results or predictions in the context of personalized medicine.Since their establishment, cell cultures have been proven to be the first and most powerful tool for the in vitro investigation of cell biology, from basic research to more complex translational approaches [6]. Classical two-dimensional (2D)-cultures usually consist of a unique type of cells (primary or continuous cultures) that grow in tissue culture polystyrene as adherent monolayers or in floating suspension, both in culture media that provide essential nutrients and growth factors. 2D-strategies are widely used to obtain a large number of cells, thus allowing the in vitro study of molecular mechanisms and development of metabolic assays [7-9]. However, due to their inability to recreate the in vivo complexity of the biological environment, they are not suitable for accurate disease modeling. These limitations have been overcome by the development of three-dimensional (3D)-cell cultures systems [10]. The rationale design of 3D-cell cultures is to harvest cells in microstructures that resemble tissues or organs shape and organization, thus allowing better cell-to-cell/cell-environment contacts and signaling crosstalk [11][12][13][14][15], essential events for tissues correct development and functioning [14,15]. The 3D-cell culture strategy is articulated in many different methods and techniques that can be grouped in scaffold-based or non-scaffold based platforms, each with particular advantages and disadvantages that make them useful for different applications [10,[16][17][18][19]. 3D-cell culture strategies are supported by the in silico...

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“…28 In the context of cancer, multicellular organoids permit the study of disease development and patient-specific response to therapy. 29 Unfortunately, these multicellular systems are scattering and aberrating, and are thus challenging to image with conventional instruments. To show the advantages of the flex-SPIM for such opaque and optically heterogenous samples, we imaged chemically fixed, agarose-embedded organoids differentiated from a patient with colorectal cancer that transgenically express nuclear-localized H2B-GFP [ Fig.…”

Section: B Light-sheet Imaging Of the Beating Zebrafish Heartmentioning

confidence: 99%

A versatile, multi-laser twin-microscope system for light-sheet imaging

Keomanee-Dizon

Fraser

Truong

2019

Preprint

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Recent developments in light-sheet microscopy techniques has led to its cutting-edge application across a range of fields, from developmental biology to behavioral neuroscience. Its low photodamage propensity allows biological dynamics to be imaged for a duration of several hours up to days; however, a tradeoff exists between such extended imaging sessions and imaging throughput, which in practice directly limits analysis workflows and the resulting time to biological discovery. Here, we present an economical instrument that can image multiple sample types simultaneously. Unlike any existing light-sheet microscope, our instrument, the flex-SPIM, shares both an ultrafast laser and a bank of continuous-wave lasers between two independently controlled light-sheet microscope-twins. Harnessing the power of modern lasers yields a substantial reduction in the cost of the light source over standard dual systems, and a doubling in imaging throughput relative to a single system. Each microscope-twin (i) operates in both one-photon and two-photon excitation modes, (ii) delivers one to three light-sheets via a trio of orthogonal excitation arms, (iii) provides sub-micron to micron imaging resolution, (iv) is multicolor compatible, and (v) permits upright and/or inverted lightsheet detection. We offer a detailed description of the flex-SPIM design to aid instrument builders who wish to construct and use a similar system. We then demonstrate the instrument's versatility for biological investigation by performing fast imaging of the beating heart in an intact zebrafish embryo, deep imaging of thick patient-derived tumor organoids, and gentle whole-brain imaging of neural activity in behaving larval zebrafish.

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Organoids for Drug Discovery and Personalized Medicine

Cited by 155 publications

References 134 publications

Diabetes through a 3D lens: organoid models

Diabetes through a 3D lens: organoid models

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

A versatile, multi-laser twin-microscope system for light-sheet imaging

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