title: Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Fredrik Eo
authors.initials: FE
authors.lastname: Holmberg
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Jakob B
authors.initials: JB
authors.lastname: Seidelin
authors.affiliation: Division of BioEngineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Cambridge, MA, USA.|Harvard Medical School, Boston, MA, USA.|Harvard Stem Cell Institute, Cambridge, MA, USA.|Harvard - MIT Division of Health Sciences and Technology, Cambridge, MA, USA.|David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Yin
authors.affiliation: Division of BioEngineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Cambridge, MA, USA.|Harvard Medical School, Boston, MA, USA.|Harvard Stem Cell Institute, Cambridge, MA, USA.|Harvard - MIT Division of Health Sciences and Technology, Cambridge, MA, USA.|David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.|Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Mead
authors.affiliation: Division of BioEngineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Cambridge, MA, USA.|Harvard Medical School, Boston, MA, USA.|Harvard Stem Cell Institute, Cambridge, MA, USA.|Harvard - MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of BioEngineering in Medicine, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Cambridge, MA, USA jmkarp@partners.org ole.haagen.nielsen@regionh.dk.|Harvard Medical School, Boston, MA, USA.|Harvard Stem Cell Institute, Cambridge, MA, USA.|Harvard - MIT Division of Health Sciences and Technology, Cambridge, MA, USA.|David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.|Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Karp
authors.affiliation: Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark jmkarp@partners.org ole.haagen.nielsen@regionh.dk.
authors.forename: Ole H
authors.identifier: 0000-0003-4612-8635
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D003470:Culture Media / Q000737:chemistry / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000628:therapy*; D007422:Intestines / Q000166:cytology* / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D019485:Bone Morphogenetic Proteins; D003470:Culture Media; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D015232:Dinoprostone
keywords: inflammatory bowel disease; intestinal stem cells; organoids; regenerative medicine; support matrix