Pluripotent stem cell derived intestinal organoids with an enteric nervous system

Loffet, Elise A; Brossard, Lisa; Mahé, Maxime M.

doi:10.1016/bs.mcb.2020.04.012

Cited by 15 publications

(9 citation statements)

References 29 publications

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“…Unified interdisciplinary efforts will be needed to further disentangle the Daedalian biology of the ENS and its cross-talk with other cellular systems [ 21 ]. Coupling such insights with in vivo gene editing strategies of candidate genes emanating from recent high-resolution transcriptomic mapping and advances in human intestinal organoids [ 307 , 308 ] together with novel live-cell imaging modalities [ 309 ] will help consolidate the current platforms to model these disorders. In addition, the development of novel ENS-based therapeutic strategies warrants human studies to confirm the clinical relevance of experimental findings.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The enteric nervous system in gastrointestinal disease etiology

Holland

Bon-Frauches

Keszthelyi

et al. 2021

Cell. Mol. Life Sci.

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A highly conserved but convoluted network of neurons and glial cells, the enteric nervous system (ENS), is positioned along the wall of the gut to coordinate digestive processes and gastrointestinal homeostasis. Because ENS components are in charge of the autonomous regulation of gut function, it is inevitable that their dysfunction is central to the pathophysiology and symptom generation of gastrointestinal disease. While for neurodevelopmental disorders such as Hirschsprung, ENS pathogenesis appears to be clear-cut, the role for impaired ENS activity in the etiology of other gastrointestinal disorders is less established and is often deemed secondary to other insults like intestinal inflammation. However, mounting experimental evidence in recent years indicates that gastrointestinal homeostasis hinges on multifaceted connections between the ENS, and other cellular networks such as the intestinal epithelium, the immune system, and the intestinal microbiome. Derangement of these interactions could underlie gastrointestinal disease onset and elicit variable degrees of abnormal gut function, pinpointing, perhaps unexpectedly, the ENS as a diligent participant in idiopathic but also in inflammatory and cancerous diseases of the gut. In this review, we discuss the latest evidence on the role of the ENS in the pathogenesis of enteric neuropathies, disorders of gut–brain interaction, inflammatory bowel diseases, and colorectal cancer.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The enteric nervous system in gastrointestinal disease etiology

Holland

Bon-Frauches

Keszthelyi

et al. 2021

Cell. Mol. Life Sci.

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“…This has been achieved for gut ENS by differentiation of PSCs under defined conditions that produce gut organoids with glial cells [ 248 ]. In another approach, the PSC-derived ENS precursor and intestinal epithelial cells are combined to form multicellular organoids [ 249 , 250 ]. To further advance this concept, the precursors of all three germ layers have been combined to form stomach and esophageal organoids with an innervated smooth muscle layer [ 251 ].…”

Section: Discussionmentioning

confidence: 99%

Schwann Cells in Digestive System Disorders

Goluba

Kunrade

Riekstiņa

et al. 2022

Cells

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Proper functioning of the digestive system is ensured by coordinated action of the central and peripheral nervous systems (PNS). Peripheral innervation of the digestive system can be viewed as intrinsic and extrinsic. The intrinsic portion is mainly composed of the neurons and glia of the enteric nervous system (ENS), while the extrinsic part is formed by sympathetic, parasympathetic, and sensory branches of the PNS. Glial cells are a crucial component of digestive tract innervation, and a great deal of research evidence highlights the important status of ENS glia in health and disease. In this review, we shift the focus a bit and discuss the functions of Schwann cells (SCs), the glial cells of the extrinsic innervation of the digestive system. For more context, we also provide information on the basic findings regarding the function of innervation in disorders of the digestive organs. We find diverse SC roles described particularly in the mouth, the pancreas, and the intestine. We note that most of the scientific evidence concerns the involvement of SCs in cancer progression and pain, but some research identifies stem cell functions and potential for regenerative medicine.

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“…62 Current models have also utilised the PSC system that can be differentiated towards intestinal organoids, as well as cells of the ENS such as neural crest cells (NCCs). [63][64][65] NCCs that were cocultured with developing intestinal organoids migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity. 63 ENS-containing intestinal organoids formed neuroglial structures similar to a myenteric and submucosal plexus in vivo.…”

Section: Innervated Organoids (Epithelial-neural Interaction)mentioning

confidence: 99%

Organoids in gastrointestinal diseases: from experimental models to clinical translation

Günther

Winner

Stappenbeck

2022

Gut

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We are entering an era of medicine where increasingly sophisticated data will be obtained from patients to determine proper diagnosis, predict outcomes and direct therapies. We predict that the most valuable data will be produced by systems that are highly dynamic in both time and space. Three-dimensional (3D) organoids are poised to be such a highly valuable system for a variety of gastrointestinal (GI) diseases. In the lab, organoids have emerged as powerful systems to model molecular and cellular processes orchestrating natural and pathophysiological human tissue formation in remarkable detail. Preclinical studies have impressively demonstrated that these organs-in-a-dish can be used to model immunological, neoplastic, metabolic or infectious GI disorders by taking advantage of patient-derived material. Technological breakthroughs now allow to study cellular communication and molecular mechanisms of interorgan cross-talk in health and disease including communication along for example, the gut–brain axis or gut–liver axis. Despite considerable success in culturing classical 3D organoids from various parts of the GI tract, some challenges remain to develop these systems to best help patients. Novel platforms such as organ-on-a-chip, engineered biomimetic systems including engineered organoids, micromanufacturing, bioprinting and enhanced rigour and reproducibility will open improved avenues for tissue engineering, as well as regenerative and personalised medicine. This review will highlight some of the established methods and also some exciting novel perspectives on organoids in the fields of gastroenterology. At present, this field is poised to move forward and impact many currently intractable GI diseases in the form of novel diagnostics and therapeutics.

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Pluripotent stem cell derived intestinal organoids with an enteric nervous system

Cited by 15 publications

References 29 publications

The enteric nervous system in gastrointestinal disease etiology

The enteric nervous system in gastrointestinal disease etiology

Schwann Cells in Digestive System Disorders

Organoids in gastrointestinal diseases: from experimental models to clinical translation

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