TY - JOUR

T1 - Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease

AU - Holmberg, Fredrik Eo

AU - Seidelin, Jakob B

AU - Yin, Xiaolei

AU - Mead, Benjamin E

AU - Tong, Zhixiang

AU - Li, Yuan

AU - Karp, Jeffrey M

AU - Nielsen, Ole H

N1 - © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Animals

KW - Bone Morphogenetic Proteins/metabolism

KW - Cell Culture Techniques/methods

KW - Culture Media/chemistry

KW - Dinoprostone/metabolism

KW - Epidermal Growth Factor/metabolism

KW - Humans

KW - Inflammatory Bowel Diseases/metabolism

KW - Intestines/cytology

KW - Receptors, Notch/metabolism

KW - Regeneration

KW - Regenerative Medicine/methods

KW - Signal Transduction

KW - Stem Cell Transplantation/methods

KW - Stem Cells/cytology

KW - Tissue Scaffolds/chemistry

KW - Transforming Growth Factor beta/metabolism

KW - Wnt Signaling Pathway

U2 - 10.15252/emmm.201607260

DO - 10.15252/emmm.201607260

M3 - Review

C2 - 28283650

VL - 9

SP - 558

EP - 570

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4676

IS - 5

ER -