Murine Models of Inflammatory Bowel Disease (IBD)

DeVoss, Jason; Diehl, Lauri

doi:10.1177/0192623313509729

Cited by 68 publications

(78 citation statements)

References 105 publications

(119 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Familiarity with the expected range and severity of lesions in the control group allows investigators to determine the validity of the results and to identify problems in the experiment should they occur. 6 In this study, we evaluated an image analysis software with predefined workflows, Tissue Studio, to develop segmentation algorithms for mouse colitis models. Software with predefined workflows are often advantageous to pathologists and scientists who do not have expertise in programming and image segmentation nor the available staff to perform such analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Tissues included entire sections of colon prepared as ''Swiss rolls'' allowing for the evaluation of the entire longitudinal section of colon. 6,11 Tissues were formalin fixed, routinely processed, paraffin embedded, sectioned, and stained with HE.…”

Section: Tissue Preparationmentioning

confidence: 99%

“…9,12 IL-10 -/-mice develop similar colonic lesions, which can be accelerated by piroxicam treatment (IL-10 -/-þ piroxicam). 3,4,6 Therefore, different mouse models are best suited to ask specific scientific or therapeutic questions and should be selected on the basis of their known molecular, cellular, and histomorphologic features and their relation to the question at hand. 6 Histologic assessment and scoring of intestinal lesions are a primary end point of many murine IBD studies.…”

mentioning

confidence: 99%

“…Histologic scoring systems are not standardized among institutions, although most scoring systems account for the severity and extent of inflammation and scores for these features are presented on an ordinal scale. 6 Most experienced pathologists develop standardized scoring systems that they use across studies; however, because histologic scoring systems are based on subjective criteria and not standardized, there is potential variability among pathologists, making meta-analyses nearly impossible.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Image Analysis-Based Approaches for Scoring Mouse Models of Colitis

Rogers¹,

Eastham-Anderson²,

DeVoss³

et al. 2015

Vet Pathol

View full text Add to dashboard Cite

Mouse models of inflammatory bowel disease are critical for basic and translational research that is advancing the understanding and treatment of this disease. Assessment of these mouse models frequently relies on histologic endpoints. In recent years, whole slide imaging and digital pathology-based image analysis platforms have become increasingly available for implementation into the pathology workflow. These automated image analysis approaches allow for nonbiased quantitative assessment of histologic endpoints. In this study, the authors sought to develop an image analysis workflow using a commercially available image analysis platform that requires minimal training in image analysis or programming, and this workflow was used to score 2 mouse models of colitis that are primarily characterized by immune cell infiltrates in the lamina propria. Although the software was unable to accurately and consistently segment hematoxylin and eosin-stained sections, automated quantification of CD3 immunolabeling resulted in strong correlations with the pathologist's score in all studies and allowed for the identification of 8 of the 9 differences among treatment groups that were identified by the pathologist. These results demonstrate not only the ability to incorporate solutions based on image analysis into the pathologist's workflow but also the importance of immunohistochemical or histochemical surrogates for the incorporation of image analysis in histologic assessments.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Tissue Preparationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Image Analysis-Based Approaches for Scoring Mouse Models of Colitis

Rogers¹,

Eastham-Anderson²,

DeVoss³

et al. 2015

Vet Pathol

View full text Add to dashboard Cite

show abstract

“…The reasons for the disconnect between preclinical studies and therapeutic efficacy have not been clearly delineated; however several possible factors are thought to be involved including: a) the use of animal models that do not adequately mimic the chronic immunopathology of human IBD, b) the use of inbred strains of mice as surrogates for heterogeneous human populations, c) differences in intestinal microbiota d) flawed experimental design and/or data analyses and e) publication bias (1–7;9). In addition to these shortcomings in the design and evaluation of preclinical studies, a particularly troubling situation has emerged over the past few years that has garnered a great deal of attention by funding agencies and the publishing community: the inability of academic and industry investigators to reproduce published studies demonstrating therapeutic efficacy of novel small molecules and biologics in animal models of disease (2;10–15). …”

Section: Introductionmentioning

confidence: 99%

Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases

Koboziev

Jones-Hall

Valentine

et al. 2015

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Animal models of disease have been used extensively by the research community for the past several decades to better understand the pathogenesis of different diseases as well as assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically-effective treatments in patients. Although several possible reasons have been suggested to account for this generalized failure to translate therapeutic efficacy from the laboratory bench to the patient’s bedside, it is becoming increasingly apparent that the mouse immune system may not adequately recapitulate the immuno-pathological mechanisms observed in human diseases. Indeed, it is well-known that >80 major differences exist between mouse and human immunology; all of which contribute to significant differences in immune system development, activation and responses to challenges in innate and adaptive immunity. This inconvenient reality has prompted investigators to attempt to humanize the mouse immune system in order to address important, human-specific questions that are impossible to study in patients. The successful long-term engraftment of human hemato-lymphoid cells in mice would provide investigators with a relatively inexpensive, small animal model to study clinically-relevant mechanisms as well as facilitate the evaluation of human-specific therapies in vivo. The discovery that targeted mutation of the IL-2 receptor common gamma chain in lymphopenic mice allows for the long-term engraftment of functional human immune cells has advanced greatly our ability to humanize the mouse immune system. The objective of this review is to present a brief overview of the recent advances that have been made in the development and use of humanized mice with special emphasis on autoimmune and chronic inflammatory diseases. In addition, we discuss current challenges and possible solutions for utilizing these unique mouse models to define the human-specific immuno-pathological mechanisms responsible for the induction and perpetuation of chronic gut inflammation.

show abstract