Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease

Research output: Contribution to journalReviewResearchpeer-review

Fredrik Eo Holmberg, Jakob B Seidelin, Xiaolei Yin, Benjamin E Mead, Zhixiang Tong, Yuan Li, Jeffrey M Karp, Ole H Nielsen

Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests that intestinal stem cell transplantation could constitute a novel treatment strategy to re-establish mucosal barrier function in patients with severe disease. Intestinal stem cells can be grownin vitroin organoid structures, though only a fraction of the cells contained are stem cells with regenerative capabilities. Hence, techniques to enrich stem cell populations are being pursued through the development of multiple two-dimensional and three-dimensional culture protocols, as well as co-culture techniques and multiple growth medium compositions. Moreover, research in support matrices allowing for efficient clinical application is in progress.In vitroculture is accomplished by modulating the signaling pathways fundamental for the stem cell niche with a suitable culture matrix to provide additional contact-dependent stimuli and structural support. The aim of this review was to discuss medium compositions and support matrices for optimal intestinal stem cell culture, as well as potential modifications to advance clinical use in IBD.

Original languageEnglish
JournalEMBO Molecular Medicine
Volume9
Issue number5
Pages (from-to)558-570
Number of pages13
ISSN1757-4676
DOIs
Publication statusPublished - 2017

    Research areas

  • Animals, Bone Morphogenetic Proteins/metabolism, Cell Culture Techniques/methods, Culture Media/chemistry, Dinoprostone/metabolism, Epidermal Growth Factor/metabolism, Humans, Inflammatory Bowel Diseases/metabolism, Intestines/cytology, Receptors, Notch/metabolism, Regeneration, Regenerative Medicine/methods, Signal Transduction, Stem Cell Transplantation/methods, Stem Cells/cytology, Tissue Scaffolds/chemistry, Transforming Growth Factor beta/metabolism, Wnt Signaling Pathway

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