Human Intestinal Organoids: Promise and Challenge

Taelman, Jasin; Dı́az, Mònica; Guiu, Jordi

doi:10.3389/fcell.2022.854740

Cited by 48 publications

(34 citation statements)

References 115 publications

(154 reference statements)

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“…Organoids are autonomous organized or reconstructed three-dimensional (3D) structures that develop from stem cells or organ-specific progenitors that aim to replicate morphology and perform similar functions to in vivo organs and tissues ( Zachos et al, 2016 ). These systems have become an important tool to simulate and study tissue morphogenesis including molecular signaling and cellular dynamics ( Hartl et al, 2019 ; Taelman et al, 2022 ). Tremendous progress has been made in the organ types and culture conditions, which can remarkably resemble the in vivo physiology more realistically than conventional two-dimensional (2D) culture.…”

Section: Recent and Novel Approaches Applied To Investigate Cellular ...mentioning

confidence: 99%

Cellular mechanisms of reverse epithelial curvature in tissue morphogenesis

Stonehouse-Smith

Cobourne

Green

et al. 2022

Front. Cell Dev. Biol.

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Epithelial bending plays an essential role during the multiple stages of organogenesis and can be classified into two types: invagination and evagination. The early stages of invaginating and evaginating organs are often depicted as simple concave and convex curves respectively, but in fact majority of the epithelial organs develop through a more complex pattern of curvature: concave flanked by convex and vice versa respectively. At the cellular level, this is far from a geometrical truism: locally cells must passively adapt to, or actively create such an epithelial structure that is typically composed of opposite and connected folds that form at least one s-shaped curve that we here, based on its appearance, term as “reverse curves.” In recent years, invagination and evagination have been studied in increasing cellular detail. A diversity of mechanisms, including apical/basal constriction, vertical telescoping and extrinsic factors, all orchestrate epithelial bending to give different organs their final shape. However, how cells behave collectively to generate reverse curves remains less well-known. Here we review experimental models that characteristically form reverse curves during organogenesis. These include the circumvallate papillae in the tongue, crypt–villus structure in the intestine, and early tooth germ and describe how, in each case, reverse curves form to connect an invaginated or evaginated placode or opposite epithelial folds. Furthermore, by referring to the multicellular system that occur in the invagination and evagination, we attempt to provide a summary of mechanisms thought to be involved in reverse curvature consisting of apical/basal constriction, and extrinsic factors. Finally, we describe the emerging techniques in the current investigations, such as organoid culture, computational modelling and live imaging technologies that have been utilized to improve our understanding of the cellular mechanisms in early tissue morphogenesis.

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Section: Recent and Novel Approaches Applied To Investigate Cellular ...mentioning

confidence: 99%

Cellular mechanisms of reverse epithelial curvature in tissue morphogenesis

Stonehouse-Smith

Cobourne

Green

et al. 2022

Front. Cell Dev. Biol.

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“…The epithelium consists of two core domains, the villus and crypts. The crypts within the epithelium contain the intestinal stem cells (ISCs), whilst the villus is composed of several differentiated cell types such as EC cells, which contain 5-HT, and enterocytes which predominantly contain the serotonin transporter (SERT) 27 . By isolating and culturing ISCs over a period of days, the stem cells divide to generate a self-renewing stem cell population, as well as cells that terminally differentiate into enterocytes, enteroendocrine cells or goblet cells (Figure 4A).…”

Section: Growth Of Organoids and Detection Of 5-ht Using Chromatograp...mentioning

confidence: 99%

“…However, these studies have been conducted on ex vivo isolated tissues, which would be challenging to sustain for high throughput studies or more recently on single cells, which lack the complexity of the mucosal epithelium. Intestinal organoids are a three-dimensional in vitro model of the intestinal epithelium that allow for robust, specific and high-throughput research of the intestinal epithelium [27][28][29] .…”

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confidence: 99%

3D Printed Electrochemical Multiwell Plate for Monitoring Food Intolerance from Intestinal Organoids

Brooks

Hussain

Kotecha

et al. 2022

Preprint

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Common symptoms of food intolerance are caused by chemical components within food that have a pharmacological activity to alter the motility of the gastrointestinal tract. Food intolerance is difficult to diagnose as it requires a long-term process of eliminating foods that are responsible for gastrointestinal symptoms. Enterochromaffin (EC) cells are key intestinal epithelium cells that respond to luminal chemical stimulants by releasing 5-HT. Changes in 5-HT levels have been shown to directly alter the motility of the intestinal tract. Therefore, a rapid approach for monitoring the impact of chemicals in food components on 5-HT levels can provide a personalised insight into food intolerance and help stratify diets. Within this study we developed a 3D printed electrochemical multiwell plate to determine changes in 5-HT levels from intestinal organoids that were exposed to varying chemical components found in food. The carbon black/poly-lactic acid (CB/PLA) electrodes had a linear range in physiological concentrations of 5-HT (0.1 – 2µM) with a limit of detection of 0.07 µM. The electrodes were stable for monitoring 5-HT overflow from intestinal organoids. Using the electrochemical multiwell plate containing intestinal organoids, increases in 5-HT were observed in the presence of 0.1 mM cinnamaldehyde and 10 mM quercetin but reduction in 5-HT levels was observed in 1 mM sorbitol when compared to control. These changes in the presence of chemicals commonly found in food were verified with ex vivo ileum tissue measurements using chromatography and amperometry with boron-doped diamond electrodes. Overall, our 3D electrochemical multiwell plate measurements with intestinal organoids highlight an approach that can be a high-throughput platform technology for rapid screening of food intolerance to provide personalised nutritional diet.

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“…The small intestines express ACE2 and TMPRSS2 in large quantities, suggesting a target for human enteric viruses [ 72 ]. Small intestinal organoids are generated from both PSC and ASC origins [ 73 ]. Small intestine organoids include enterocytes, goblet cells, enteroendocrine cells, transit amplifying cells, and stem cells [ 74 ].…”

Section: Other Organoids Relevant For Sars-cov-2 Disease Modelingmentioning

confidence: 99%

Organoid Technologies for SARS-CoV-2 Research

et al. 2022

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Purpose of Review Organoids are an emerging technology utilizing three-dimensional (3D), multi-cellular in vitro models to represent the function and physiological responses of tissues and organs. By using physiologically relevant models, more accurate tissue responses to viral infection can be observed, and effective treatments and preventive strategies can be identified. Animals and two-dimensional (2D) cell culture models occasionally result in inaccurate disease modeling outcomes. Organoids have been developed to better represent human organ and tissue systems, and accurately model tissue function and disease responses. By using organoids to study SARS-Cov-2 infection, researchers have now evaluated the viral effects on different organs and evaluate efficacy of potential treatments. The purpose of this review is to highlight organoid technologies and their ability to model SARS-Cov-2 infection and tissue responses. Recent Findings Lung, cardiac, kidney, and small intestine organoids have been examined as potential models of SARS-CoV-2 infection. Lung organoid research has highlighted that SARS-CoV-2 shows preferential infection of club cells and have shown value for the rapid screening and evaluations of multiple anti-viral drugs. Kidney organoid research suggests human recombinant soluble ACE2 as a preventative measure during early-stage infection. Using small intestine organoids, fecal to oral transmission has been evaluated as a transmission route for the virus. Lastly in cardiac organoids drug evaluation studies have found that drugs such as bromodomain, external family inhibitors, BETi, and apabetalone may be effective treatments for SARs-CoV-2 cardiac injury. Summary Organoids are an effective tool to study the effects of viral infections and for drug screening and evaluation studies. By using organoids, more accurate disease modeling can be performed, and physiological effects of infection and treatment can be better understood.

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Human Intestinal Organoids: Promise and Challenge

Cited by 48 publications

References 115 publications

Cellular mechanisms of reverse epithelial curvature in tissue morphogenesis

Cellular mechanisms of reverse epithelial curvature in tissue morphogenesis

3D Printed Electrochemical Multiwell Plate for Monitoring Food Intolerance from Intestinal Organoids

Organoid Technologies for SARS-CoV-2 Research

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