High-resolution 3D imaging of fixed and cleared organoids

Dekkers, Johanna F.; Alieva, María; Wellens, Lianne M.; Ariese, Hendrikus C R; Jamieson, Paul; Vonk, Annelotte M.; Amatngalim, Gimano D.; Hu, Huili; Oost, Koen C.; Snippert, Hugo J.G.; Beekman, Jeffrey M.; Wehrens, Ellen J.; Visvader, Jane E.; Clevers, Hans; Rios, Anne C.

doi:10.1038/s41596-019-0160-8

Cited by 400 publications

(303 citation statements)

References 36 publications

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“…As a result, the application of intestinal organoids is limited especially in the field of regenerative medicine (Huang, Ren, Wu, Li, & Ren, ). Additionally, morphological and functional evaluations of intestinal organoids are mainly dependent on the 3D imaging that usually involves the organoid fixation (Dekkers et al, ). Unfortunately, this procedure causes the death of intestinal organoids and hinders observation of organoid development.…”

Section: Introductionmentioning

confidence: 99%

Biomaterials and biosensors in intestinal organoid culture, a progress review

Huang

Jiang

Ren

et al. 2020

J Biomedical Materials Res

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As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their threedimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them. K E Y W O R D Sbiosensor, intestinal stem cell, organoid, regenerative medicine, scaffold design

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Section: Introductionmentioning

confidence: 99%

Biomaterials and biosensors in intestinal organoid culture, a progress review

Huang

Jiang

Ren

et al. 2020

J Biomedical Materials Res

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“…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. For example, organoids can easily be manipulated using viral and nonviral mediated delivery of CRISPR-Cas9 gene editing [22], they can be investigated using mass spectrometry [23], flow cytometry [24], multiple single cell 'omics' technologies [25] and naturally their 3D structure lends themselves to all manner of imaging technologies [26] (Fig. 1).…”

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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“…However, most conventional OPT imaging systems lack cellular resolution and cannot delineate between neighboring tissue elements in large samples at low resolution (i.e., after E16.5 in mice). The recent advent of light sheet microscopy holds considerable promise in addressing the limitations in both systems and consequently has been recently employed to examine both cellular resolution and whole tissue morphology in organs and organoids (Dekkers et al, 2019;Hasegawa et al, 2019).…”

Section: Imaging Branching Morphogenesismentioning

confidence: 99%

Branching morphogenesis as a driver of renal development

Short

Smyth

2020

The Anatomical Record

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Branching morphogenesis is an integral developmental mechanism central to the formation of a range of organs including the kidney, lung, pancreas and mammary gland. The ramified networks of epithelial tubules it establishes are critical for the processes of secretion, excretion and exchange mediated by these tissues. In the kidney, branching serves to establish the collecting duct system that transports urine from the nephrons into the renal pelvis, ureter and finally the bladder. Generally speaking, the formation of these networks in different organs begins with the specification and differentiation of simple bud‐like organ anlage, which then undergo a process of elaboration, typically by bifurcation. This process is often governed by the interaction of progenitor cells at the tips of the epithelia with neighboring mesenchymal cell populations which direct the branching process and which often themselves differentiate to form part of the adult organ. In the kidney, the tips of ureteric bud elaborate through a dynamic cell signaling relationship with overlying nephron progenitor cell populations. These cells sequentially commit to differentiation and the resulting nephrons reintegrate with the ureteric epithelium as development progresses. This review will describe recent advances in understanding the how the elaboration of the ureteric bud is patterned and consider the extent to which this process is shared with other organs.

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High-resolution 3D imaging of fixed and cleared organoids

Cited by 400 publications

References 36 publications

Biomaterials and biosensors in intestinal organoid culture, a progress review

Biomaterials and biosensors in intestinal organoid culture, a progress review

Diabetes through a 3D lens: organoid models

Branching morphogenesis as a driver of renal development

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