Modeling Intestinal Stem Cell Function with Organoids

Takahashi, Toshio; Fujishima, Kazuto; Kengaku, Mineko

doi:10.3390/ijms222010912

Cited by 23 publications

(21 citation statements)

References 102 publications

(146 reference statements)

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“…Intestinal organoids techniques have become a powerful tool for studying the interaction between microbiota and the intestinal mucosal barrier. 42 , 43 To further explore the intestinal epithelium- lactobacillus interactions, enteroids were applied in our study in vitro . Paneth cells of small intestine are located at the base of intestinal crypts, intercalated among the active intestinal stem cells.…”

Section: Discussionmentioning

confidence: 99%

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency

Mei

Huang

et al. 2022

Gut Microbes

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Toll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. L. reuteri treatment was carried out in vivo and vitro study. Compared with wild-type mice, AP and AP-associated gut injury were exacerbated in TLR4ΔIEC mice in a gut microbiota-dependent manner. The relative abundance of Lactobacillus and number of Paneth cells remarkably decreased in TLR4ΔIEC mice. The KEGG pathway analysis derived from RNA sequencing suggested that genes affected by intestinal TLR4 deletion were related to the activation of nod-like receptor pathway. Furthermore, L. reuteri treatment could significantly improve the pancreatic and intestinal injury in TLR4ΔIEC mice through promoting Paneth cells in a NOD2-dependent manner. Loss of intestinal epithelial TLR4 exacerbated pancreatic and intestinal damage during AP, which might be attributed to the gut microbiota dysbiosis especially the exhausted Lactobacillus. L. reuteri might maintain intestinal homeostasis and alleviate AP via Paneth cells modulation. Abbreviations: AP Acute pancreatitis, TLR4 Toll-like receptor 4, IL-1β Interleukin-1β, IL-6 Interleukin-6, TNF-α Tumor necrosis factor-α, SIRS Systematic inflammatory response syndrome, LPS Lipopolysaccharides, SPF Specific pathogen-free, ZO-1 Zonula occludens-1, CON Control, H&E Hematoxylin and eosin, FISH Fluorescence in situ hybridization, DAPI 4′,6-diamidino-2-phenylindole, PCoA Principal co-ordinates analysis, SCFA Short chain fatty acid, LEfSe Linear discriminant analysis Effect Size, ANOVA Analysis of variance, F/B Firmicutes/Bacteroidetes, PCA Principal component analysis, NOD2 Nod-like receptor 2, ABX antibiotics, PCNA proliferating cell nuclear antigen

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Section: Discussionmentioning

confidence: 99%

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency

Mei

Huang

et al. 2022

Gut Microbes

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“…Although there has been no single model that can investigate human GI biology as a whole, organ-like culture derived from stem cells, or organoids, are considered an elegant model as it can recapitulate the cellular diversity in a 3D structure and can expand in vitro long term. For example, gut organoids can include multiple differentiated epithelial cell types such as enterocytes, Paneth, goblet, and enteroendocrine cells and can be incorporated into systems with nonepithelial cell types, such as immune cells [ 149 ]. Gut epithelium and the associated mucin gel are the primary sites for gut microbial communities as well as major barriers for pathogen invasion into the GI tract [ 150 ].…”

Section: Materials-enabled New Models For Studying Human Gut Microbiomementioning

confidence: 99%

Material Engineering in Gut Microbiome and Human Health

et al. 2022

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Tremendous progress has been made in the past decade regarding our understanding of the gut microbiome’s role in human health. Currently, however, a comprehensive and focused review marrying the two distinct fields of gut microbiome and material research is lacking. To bridge the gap, the current paper discusses critical aspects of the rapidly emerging research topic of “material engineering in the gut microbiome and human health.” By engaging scientists with diverse backgrounds in biomaterials, gut-microbiome axis, neuroscience, synthetic biology, tissue engineering, and biosensing in a dialogue, our goal is to accelerate the development of research tools for gut microbiome research and the development of therapeutics that target the gut microbiome. For this purpose, state-of-the-art knowledge is presented here on biomaterial technologies that facilitate the study, analysis, and manipulation of the gut microbiome, including intestinal organoids, gut-on-chip models, hydrogels for spatial mapping of gut microbiome compositions, microbiome biosensors, and oral bacteria delivery systems. In addition, a discussion is provided regarding the microbiome-gut-brain axis and the critical roles that biomaterials can play to investigate and regulate the axis. Lastly, perspectives are provided regarding future directions on how to develop and use novel biomaterials in gut microbiome research, as well as essential regulatory rules in clinical translation. In this way, we hope to inspire research into future biomaterial technologies to advance gut microbiome research and gut microbiome-based theragnostics.

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“…Neuronal innervation is an essential part of an organ that regulates various biological processes. For example, acetylcholine (ACh) is a neurotransmitter that triggers cholinergic signaling which plays a pivotal role in the regulation of the small intestine cells [96]. A study conducted by Workman et al tried to provide the solution to this problem by introducing the hPSCs derived-neural crest cells (NCC) to hPSCs-derived intestinal organoids [97].…”

Section: Tissue Complexitymentioning

confidence: 99%

Strategies for Generating Human Pluripotent Stem Cell- Derived-Organoid Culture for Disease Modelling, Drug Screening, and Regenerative Therapy

Gania¹,

Noorintan²,

Septiari³

et al. 2022

Preprint

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Human pluripotent stem cells (hPSCs) have become a powerful tool to generate various kinds of cell types comprising the human body. Recently, organoid technology emerged as a platform to build a physiologically relevant tissue-like structure from the PSCs, which provides a more relevant three-dimensional microenvironment to the actual human body than the conventional monolayer culture system for transplantation, disease modeling, and drug development. Although it holds so many advantages, the organoid culture system still has various problems related to culture methods, which became a challenge to get similar physiological properties to their original tissue counterparts. Here, we discuss the current development of organoid culture methods, including the problem that may arise from the currently available culture systems as well as the possible approach to overcoming the current limitation and improving their optimum utilization for translational application purposes.

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Modeling Intestinal Stem Cell Function with Organoids

Cited by 23 publications

References 102 publications

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency

Material Engineering in Gut Microbiome and Human Health

Strategies for Generating Human Pluripotent Stem Cell- Derived-Organoid Culture for Disease Modelling, Drug Screening, and Regenerative Therapy

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