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Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems

Hartman, KG and Bortner, JD and Falk, GW and Yu, J and Martín, MG and Rustgi, AK and Lynch, JP (2013) Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems. Stem Cell Research and Therapy, 4 (SUPPL.).

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Abstract

Gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), graft-versus-host disease (GVHD), and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are common human gastrointestinal diseases that share inflammation as a key driver for their development. A general outcome resulting from these chronic inflammatory conditions is increased oxidative stress. Oxidative stress is caused by the generation of reactive oxygen and nitrogen species that are part of the normal inflammatory response, but are also capable of damaging cellular DNA, protein, and organelles. Damage to DNA can include DNA strand breaks, point mutations due to DNA adducts, as well as alterations in methylation patterns leading to activation of oncogenes or inactivation of tumor suppressors. There are a number of significant long-term consequences associated with chronic oxidative stress, most notably cancer. Infiltrating immune cells and stromal components of tissue including fibroblasts contribute to dynamic changes occurring in tissue related to disease development. Immune cells can potentiate oxidative stress, and fibroblasts have the capacity to contribute to advanced growth and proliferation of the epithelium and any resultant cancers. Disease models for GERD, BE, GVHD, and ulcerative colitis based on three-dimensional human cell and tissue culture systems that recapitulate in vivo growth and differentiation in inflammatory-associated microphysiological environments would enhance our understanding of disease progression and improve our ability to test for disease-prevention strategies. The development of physiologically relevant, human cell-based culture systems is therefore a major focus of our research. These novel models will be of enormous value, allowing us to test hypotheses and advance our understanding of these disorders, and will have a translational impact allowing us to more rapidly develop therapeutic and chemopreventive agents. In summary, this work to develop advanced human cell-based models of inflammatory conditions will greatly improve our ability to study, prevent, and treat GERD, BE, GVHD, and inflammatory bowel disease. The work will also foster the development of novel therapeutic and preventive strategies that will improve patient care for these important clinical conditions. © 2013 BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hartman, KG
Bortner, JD
Falk, GW
Yu, Jjiy3@pitt.eduJIY3
Martín, MG
Rustgi, AK
Lynch, JP
Centers: Other Centers, Institutes, or Units > Hillman Cancer Center
Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 20 December 2013
Date Type: Publication
Journal or Publication Title: Stem Cell Research and Therapy
Volume: 4
Number: SUPPL.
DOI or Unique Handle: 10.1186/scrt366
Schools and Programs: School of Medicine > Pathology
School of Medicine > Radiation Oncology
Refereed: Yes
Article Type: Review
Date Deposited: 02 Dec 2016 20:17
Last Modified: 04 Mar 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/29628

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