A new organotypic model to study cell interactions in the intestinal mucosa

Spöttl, T.; Hausmann, Martin; Gunckel, Manuela; Herfarth, Hans H; Herlyn, Meenhard; Schöelmerich, Juergen; Rogler, Gerhard

doi:10.1097/00042737-200608000-00017

Cited by 17 publications

(18 citation statements)

References 33 publications

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“…The treatment options, however are still rather symptomatic than curative. Therefore, recently developed co-culture models involving cells of the immune system like monocytes, macrophages or dendritic cells could aid in understanding the role of certain cell types in these diseases, and in the development of novel treatment strategies (Leonard et al, 2010(Leonard et al, , 2012Spottl et al, 2006). Similarly, autologous, humanized primary co-culture models (H. Walles lab, unpublished data) constitute a further improvement for the development and testing of new vaccines for more efficient and individualized treatment of gastrointestinal cancers, which show an extremely high prevalence worldwide.…”

Section: Co-culture and Pathophysiological Modelsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

122

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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Section: Co-culture and Pathophysiological Modelsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

122

103

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“…4e) further sustain this hypothesis 38 . The capacity of intestinal cells to promote an anergic polarization of macrophages has been suggested in previous studies that used intestinal cell lines 31 . Further characterization of co-cultured macrophages, including their phenotype and other effector functions in steady state and during infection is warranted to better understand their functional phenotype and contribution to host homeostasis and immune defenses.…”

Section: Discussionmentioning

confidence: 90%

“…Caco-2 and HT-29) 7,8,[31][32][33][34] , the macrophage-enteroid model we established was based exclusively on primary human cells. Also, unlike existing cancer cell models, the enteroids that provide the framework for the macrophage-intestinal epithelium co-culture naturally exhibit the major cell types found within intestinal epithelium in vivo, as shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

A Primary Human Macrophage-Enteroid Co-Culture Model to Investigate Mucosal Gut Physiology and Host-Pathogen Interactions

Baetz¹,

Noël²,

Staab³

et al. 2017

Gastroenterology

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“…Several cell culture models incorporating immunocompetent cells, such as macrophages or B-cells, to simulate intestinal tissue have been developed (tanoue et al, 2008;des Rieux et al, 2007;Spottl et al, 2006). In our model, the inflammatory response is promoted by addition of a pro-inflammatory cytokine to the triple culture of epithelial and immunocompetent cells to mimic the inflammation in IBD.…”

Section: Discussionmentioning

confidence: 99%

“…All cells in the model are of human origin, eliminating the issues with species differences often associated with the different animal models. During 21 days of co-culture to allow tight barrier formation, immune cells assume an intestinal phenotype (Spottl et al, 2006). the incorporation of immunocompetent cells is crucial for the inflammation stimulation.…”

Section: Introductionmentioning

confidence: 99%

Screening of budesonide nanoformulations for treatment of inflammatory bowel disease in an inflamed 3D cell-culture model

Leonard

Ali²,

Collnot

et al. 2012

ALTEX

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Summary Drug formulation screenings for treatment of inflammatory bowel disease (IBD) are mostly conducted in chemically induced rodent models that represent acute injury-caused inflammation instead of a chronic condition. To accurately screen drug formulations for chronic IBD, a relevant model that mimics the chronic condition in vitro is urgently needed. In an effort to reduce and potentially replace this scientifically and ethically questionable animal testing for IBD drugs, our laboratory has developed an in vitro model for the inflamed intestinal mucosa observed in chronic IBD, which allows high-throughput screening of anti-inflammatory drugs and their formulations. The in vitro model consists of intestinal epithelial cells, human blood-derived macrophages, and dendritic cells that are stimulated by the inflammatory cytokine interleukin-1β. In this study, the model was utilized for evaluation of the efficacy and deposition of budesonide, an anti-inflammatory drug, in three different pharmaceutical formulations: (1) a free drug solution, (2) encapsulated into PLGA nanoparticles, and (3) encapsulated into liposomes. The in vitro model of the inflamed intestinal mucosa demonstrated its ability to differentiate therapeutic efficacy among the formulations while maintaining the convenience of conventional in vitro studies and adequately representing the complex pathophysiological changes observed in vivo.

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A new organotypic model to study cell interactions in the intestinal mucosa

Abstract: In the three-dimensional organotypic cell culture model monocytes differentiate into intestinal-like macrophages when co-cultured with control intestinal fibroblasts and intestinal epithelial cells. Intestinal epithelial cells may be necessary for differentiation of intestinal macrophages.

Cited by 17 publications

References 33 publications

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

A Primary Human Macrophage-Enteroid Co-Culture Model to Investigate Mucosal Gut Physiology and Host-Pathogen Interactions

Screening of budesonide nanoformulations for treatment of inflammatory bowel disease in an inflamed 3D cell-culture model

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