Engineering organoids

Hofer, Moritz; Lütolf, Matthias P.

doi:10.1038/s41578-021-00279-y

Cited by 646 publications

(615 citation statements)

References 278 publications

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“…Therefore, it is important to consider the suitability of a differentiation and maturation technique for any desired endpoints. Although organoid models may be more relevant, they may limit throughput due to added complexity of the culture format and a limited number of compatible assays [ 37 , 184 ]. They can also add additional complexity when it comes to dosing, penetration, and consistency between replicates due to the presence of multiple cell types in varied proportions [ 185 , 186 ].…”

Section: Discussionmentioning

confidence: 99%

Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?

McKnight

Low

Elliott

et al. 2021

IJMS

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Mitochondrial diseases disrupt cellular energy production and are among the most complex group of inherited genetic disorders. Affecting approximately 1 in 5000 live births, they are both clinically and genetically heterogeneous, and can be highly tissue specific, but most often affect cell types with high energy demands in the brain, heart, and kidneys. There are currently no clinically validated treatment options available, despite several agents showing therapeutic promise. However, modelling these disorders is challenging as many non-human models of mitochondrial disease do not completely recapitulate human phenotypes for known disease genes. Additionally, access to disease-relevant cell or tissue types from patients is often limited. To overcome these difficulties, many groups have turned to human pluripotent stem cells (hPSCs) to model mitochondrial disease for both nuclear-DNA (nDNA) and mitochondrial-DNA (mtDNA) contexts. Leveraging the capacity of hPSCs to differentiate into clinically relevant cell types, these models permit both detailed investigation of cellular pathomechanisms and validation of promising treatment options. Here we catalogue hPSC models of mitochondrial disease that have been generated to date, summarise approaches and key outcomes of phenotypic profiling using these models, and discuss key criteria to guide future investigations using hPSC models of mitochondrial disease.

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Section: Discussionmentioning

confidence: 99%

Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?

McKnight

Low

Elliott

et al. 2021

IJMS

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“…37,38 Controlling organoid morphology is a sought-after goal, which has been mostly interpreted as requiring spatiotemporal control of gene expression, for which optogenetic approaches have been suggested. 39 Yet, the spatiotemporally-localized application of photochemical compounds offers an alternative, in which the possibility of instantaneous cellular response to stimulus is highly attractive for temporally-precise control. Based on the good performance of SBTubA4P in 2D cell culture, we assessed whether SBTubA4P can be controlled similarly precisely in a 3D organoid model, aiming to manipulate organoid development by locally interfering with the invasion of individual branches during the elongation phase 38 .…”

Section: Sbtub Photocontrol In 3d Organoids Enables Spatially-targetementioning

confidence: 99%

In vivo photocontrol of microtubule dynamics and integrity, migration and mitosis, by the potent GFP-imaging-compatible photoswitchable reagents SBTubA4P and SBTub2M

Gao

Meiring

Varady

et al. 2021

Preprint

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Photoswitchable reagents to modulate microtubule stability and dynamics are an exciting tool approach towards micron- and millisecond-scale control over endogenous cytoskeleton-dependent processes. When these reagents are globally administered yet locally photoactivated in 2D cell culture, they can exert precise biological control that would have great potential for in vivo translation across a variety of research fields and for all eukaryotes. However, photopharmacology's reliance on the azobenzene photoswitch scaffold has been accompanied by a failure to translate this temporally- and cellularly-resolved control to 3D models or to in vivo applications in multi-organ animals, which we attribute substantially to the metabolic liabilities of azobenzenes. Here, we optimised the potency and solubility of metabolically stable, druglike colchicinoid microtubule inhibitors based instead on the styrylbenzothiazole (SBT) photoswitch scaffold, that are non-responsive to the major fluorescent protein imaging channels and so enable multiplexed imaging studies. We applied these reagents to 3D systems (organoids, tissue explants) and classic model organisms (zebrafish, clawed frog) with one- and two-protein imaging experiments. We successfully used systemic treatment plus spatiotemporally-localised illuminations in vivo to photocontrol microtubule dynamics, network architecture, and microtubule-dependent processes in these systems with cellular precision and second-level resolution. These nanomolar, in vivo-capable photoswitchable reagents can prove a game-changer for high-precision cytoskeleton research in cargo transport, cell motility, cell division and development. More broadly, their straightforward design can also inspire the development of similarly capable optical reagents for a range of protein targets, so bringing general in vivo photopharmacology one step closer to productive realisation.

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“…Organoids maintain great potentials for their application in regenerative medicine. Scientists have already started using this technology to repair damaged organs (Sampaziotis et al 2021 ; Grassi et al 2019 ; Nakamura and Sato 2018 ; Hofer and Lutolf 2021 ). For example, Sampaziotis et al uccessfully repair bile ducts by engrafting cholangiocyte organoids into injured human liver (Sampaziotis et al 2021 ).…”

Section: Perspectivesmentioning

confidence: 99%

Defense of COVID-19 by Human Organoids

Meng

et al. 2021

Phenomics

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has created an immense menace to public health worldwide, exerting huge effects on global economic and political conditions. Understanding the biology and pathogenesis mechanisms of this novel virus, in large parts, relies on optimal physiological models that allow replication and propagation of SARS-CoV-2. Human organoids, derived from stem cells, are three-dimensional cell cultures that recapitulate the cellular organization, transcriptional and epigenetic signatures of their counterpart organs. Recent studies have indicated their great values as experimental virology platforms, making human organoid an ideal tool for investigating host-pathogen interactions. Here, we summarize research developments for SARS-CoV-2 infection of various human organoids involved in multiple systems, including lung, liver, brain, intestine, kidney and blood vessel organoids. These studies help us reveal the pathogenesis mechanism of COVID-19, and facilitate the development of effective vaccines and drugs as well as other therapeutic regimes.

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Engineering organoids

Cited by 646 publications

References 278 publications

Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?

Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?

In vivo photocontrol of microtubule dynamics and integrity, migration and mitosis, by the potent GFP-imaging-compatible photoswitchable reagents SBTubA4P and SBTub2M

Defense of COVID-19 by Human Organoids

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