Fibroblasts and myofibroblasts of the intestinal lamina propria in physiology and disease

Roulis, Manolis; Flavell, Richard A.

doi:10.1016/j.diff.2016.05.002

Cited by 187 publications

(150 citation statements)

References 123 publications

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“…Alternatively, the mesenchyme may still potentiate regenerative responses in villus damage. Such close communication between epithelial and mesenchymal WNT signaling pathways has been shown in both the Drosophila midgut as well as mammalian small intestine (Kux and Pitsouli, 2014; Le Guen et al, 2015; Roulis and Flavell, 2016; Karlsson et al, 2000). Well-established feedback loops from Hedgehog and WNT signal pathways could serve as a potential link between the mesenchyme and the epithelium after RV infection (Büller et al, 2012; Kosinski et al, 2010).…”

Section: Discussionmentioning

confidence: 93%

Epithelial WNT Ligands Are Essential Drivers of Intestinal Stem Cell Activation

et al. 2018

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SUMMARY Intestinal stem cells (ISCs) maintain and repair the intestinal epithelium. While regeneration after ISC-targeted damage is increasingly understood, injury-repair mechanisms that direct regeneration following injuries to differentiated cells remain uncharacterized. The enteric pathogen, rotavirus, infects and damages differentiated cells while sparing all ISC populations, thus allowing the unique examination of the response of intact ISC compartments during injury-repair. Upon rotavirus infection in mice, ISC compartments robustly expand and proliferating cells rapidly migrate. Infection results specifically in stimulation of the active crypt-based columnar ISCs, but not alternative reserve ISC populations, as is observed after ISC-targeted damage. Conditional ablation of epithelial WNT secretion diminishes crypt expansion and ISC activation, demonstrating a previously unknown function of epithelial-secreted WNT during injury-repair. These findings indicate a hierarchical preference of crypt-based columnar cells (CBCs) over other potential ISC populations during epithelial restitution and the importance of epithelial-derived signals in regulating ISC behavior.

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Section: Discussionmentioning

confidence: 93%

Epithelial WNT Ligands Are Essential Drivers of Intestinal Stem Cell Activation

et al. 2018

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“…In an attempt to rescue the cat enteroids, we supplemented 50% L-WRN CM with various factors that have been shown to induce enteroid growth in other platforms or to be secreted by mesenchymal/stromal cells within the crypt niche (Fig. 3) (Date and Sato, 2015; Roulis and Flavell, 2016). These factors included: ALK5 inhibitor A83-01 and p38 MAP kinase inhibitor SB202190 (Khalil et al, 2016; Sato et al, 2011a), human FGF-4 (Clevers, 2016; McCracken et al, 2014; Spence et al, 2011), human FGF-2 (FGF-basic) (Clevers, 2016), human FGF-10 and nicotinamide (Barker et al, 2010; Boj et al, 2015; Sato and Clevers, 2015), human IGF-I (Reynolds et al, 2014; Simmons et al, 2007), Prostaglandin E2 (PGE2) (Goessling et al, 2009; Jung et al, 2011; Pierzchalska et al, 2012), or mouse Wnt-2b and human Gremlin (Aoki et al, 2016; Stzepourginski et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals

2017

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Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN). Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. LF/SC enteroids expressed crypt stem cell marker LGR5 and low levels of mesenchymal marker VIM. Labeling with EdU also showed distinct regions of cell proliferation within the enteroids marking crypt-like regions. The ability to grow and maintain LF/SC enteroid cell lines provides additional models for the study of gastrointestinal developmental biology as well as platforms for the study of host-pathogen interactions between intestinal cells and zoonotic enteric pathogens of medical importance.

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“…Myofibroblasts are located under a basement membrane in the crypt, which promote stem cell self-renewal and differentiation [19]. In addition, myofibroblasts provide trophic substances to stem cells via secretion of proteins including transforming growth factor (TGF)- β [20].…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Novel Model for Anticancer Drug Resistance in Three‐Dimensional Primary Culture of Tumor Microenvironment

Usui

Sakurai

Enjoji

et al. 2016

Stem Cells International

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Tumor microenvironment has been implicated in tumor development and progression. As a three-dimensional tumor microenvironment model, air liquid interface (ALI) organoid culture from oncogene transgenic mouse gastrointestinal tissues was recently produced. However, ALI organoid culture system from tissues of colorectal cancer patients has not been established. Here, we developed an ALI organoid model from normal and tumor colorectal tissues of human patients. Both organoids were successfully generated and showed cystic structures containing an epithelial layer and surrounding mesenchymal stromal cells. Structures of tumor organoids closely resembled primary tumor epithelium. Expression of an epithelial cell marker, E-cadherin, a goblet cell marker, MUC2, and a fibroblast marker, vimentin, but not a myofibroblast marker, α-smooth muscle actin (SMA), was observed in normal organoids. Expression of E-cadherin, MUC2, vimentin, and α-SMA was observed in tumor organoids. Expression of a cancer stem cell marker, LGR5 in tumor organoids, was higher than that in primary tumor tissues. Tumor organoids were more resistant to toxicity of 5-fluorouracil and Irinotecan than colorectal cancer cell lines, SW480, SW620, and HCT116. These findings indicate that ALI organoid culture from colorectal cancer patients may become a novel model that is useful for examining resistance to chemotherapy in tumor microenvironment.

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Fibroblasts and myofibroblasts of the intestinal lamina propria in physiology and disease

Cited by 187 publications

References 123 publications

Epithelial WNT Ligands Are Essential Drivers of Intestinal Stem Cell Activation

Epithelial WNT Ligands Are Essential Drivers of Intestinal Stem Cell Activation

WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals

Establishment of a Novel Model for Anticancer Drug Resistance in Three‐Dimensional Primary Culture of Tumor Microenvironment

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