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 - 2017/5
Y1 - 2017/5
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
SN - 1757-4676
VL - 9
SP - 558
EP - 570
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 5
ER -
