Stem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium

Flier, Laurens G. van der; Clevers, Hans

doi:10.1146/annurev.physiol.010908.163145

Cited by 1,543 publications

(1,349 citation statements)

References 123 publications

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“…Such a broad lining of the body surface largely exceeds that of skin, and constitutes the largest frontline to the outer-body environment. To confront and cope with the continuous but dynamic change of the surrounding environment, the intestinal epithelia is completely renewed within a short period, reaching up to every 4-5 days in the small intestine [10].…”

Section: Homeostasis Of the Normal Intestinal Epitheliamentioning

confidence: 99%

Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease

2015

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In the past decades, continuous effort has been paid to deeply understanding the pathophysiology of inflammatory bowel diseases (IBD), such as ulcerative colitis or Crohn's disease. As the disease typically arises as chronic inflammation of the gastrointestinal mucosa, research has been focused on how such an uncontrolled, deleterious immune response may arise and persist in a certain cohort of patients. Based on those immunologic analyses, the establishment of anti-TNF-a therapy, and the following series of biologic agents achieved great success and dramatically changed the therapeutic strategy of IBD patients. However, to guarantee long-term remission of the disease, the therapeutic standard has been raised to achieve ''mucosal healing'', which requires complete repair of the gastrointestinal mucosa. Recent studies have revealed the unexpected importance of epithelial cells in the pathophysiology of IBD. The general barrier function as well as the cell lineage-specific functions have been deeply attributed to the development of chronic intestinal inflammation. Also, the groundbreaking establishment of the in vitro intestinal stem cell culture system has opened up a way of developing stem cell transplantation therapy to treat otherwise refractory ulcers that may persist in IBD patients. In this review, we would like to focus on the role of epithelial cells in the pathophysiology of IBD, and also give a perspective to the upcoming development of regenerative therapies that may become one of the therapeutic choices to achieve mucosal healing in refractory patients of IBD.

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Section: Homeostasis Of the Normal Intestinal Epitheliamentioning

confidence: 99%

Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease

2015

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“…85, 2011 NOTES 7945 nal tissue, which has the highest turnover rate of all adult mammalian tissues (24,65). This speculation is also supported by the fact that the fastest-evolving nonenterovirus, HPeV, frequently infects enteric tissue (15,56) and was once classified as an enterovirus (15,56).…”

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confidence: 98%

Genus-Specific Substitution Rate Variability among Picornaviruses

Hicks

Duffy

2011

J Virol

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Picornaviruses have some of the highest nucleotide substitution rates among viruses, but there have been no comparisons of evolutionary rates within this broad family. We combined our own Bayesian coalescent analyses of VP1 regions from four picornaviruses with 22 published VP1 rates to produce the first within-family meta-analysis of viral evolutionary rates. Similarly, we compared our rate estimates for the RNA polymerase 3D pol gene from five viruses to four published 3D pol rates. Both a structural and a nonstructural gene show that enteroviruses are evolving, on average, a half order of magnitude faster than members of other genera within the Picornaviridae family.Members of the Picornaviridae family are the most common cause of human viral infections in developed countries (28,39). Human picornaviruses produce symptoms ranging from mild respiratory illness to hemorrhagic conjunctivitis, myocarditis, acute flaccid paralysis, and neonatal organ failure (19,27,28,33,40,41). Veterinary picornaviruses, such as foot-and-mouth disease virus (FMDV), encephalomyocarditis virus (EMCV), and porcine teschovirus (PTV), can have devastating effects on livestock (5,8,21).Although picornaviruses such as poliovirus (PV) are known to evolve more rapidly than other viruses with single-stranded RNA (ssRNA) genomes (9, 29), little research has been conducted to investigate how they evolve more rapidly than other viruses with similarly error-prone RNA-dependent RNA polymerases (29, 57) or if certain picornaviruses evolve more rapidly than others. Understanding the evolutionary potentials and constraints of these important pathogens is imperative for the development of durable vaccines and effective treatment plans for individual pathogens (42). As even small, 3-fold differences in RNA virus mutation rates can have dramatic consequences, such as driving a population into lethal mutagenesis (7), similar differences in long-term evolutionary rates could indicate significantly dissimilar evolutionary potentials.While viral evolutionary rates were previously calculated only by linear regression, modern simulation software such as BEAST (11) allows for the estimation of more complex models of viral evolution. These Bayesian coalescent programs can produce both estimated mean rates of evolution and 95% credibility intervals (CIs) that provide a measure of the variability around mean rates. Instead of comparing single-point estimates, now nonoverlapping CIs provide the strongest evidence that genes or organisms are evolving at different rates (11). Many substitution rate estimates have been published for picornaviruses, especially for the antigenically significant VP1 gene, which encodes the most external of the picornavirus structural proteins and interacts with cellular receptors (37,49). Based on sequence availability in GenBank, four novel analyses were conducted, measuring the rate of evolution of the VP1 gene for two enteroviruses and producing the first rate estimates for the type species of the genera Cardiovirus and Teschoviru...

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“…The intestinal epithelium has been reported to have a self-renewal characteristic in vivo [18,34,35]. In recent reports, the intestinal epithelium could be isolated from the organ and culture in vitro, and cultured cells have retained their characteristics [21,25].…”

Section: Discussionmentioning

confidence: 99%

“…[17] However, Paneth cells can survive at the bottom of the crypt for approximately 6 weeks. [18] Lgr5-expressing stem cells also exist in the bottom of crypt and supply the differentiated cells to maintain the balance among these 4 types of cells. [19] In this manner, intestinal epithelium constantly repeats self-renewal for maintaining their function and treating damage to the epithelium due to radiation, inflammation, etc.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2017

RJLBPCS

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ABSTRACT:The aim of this study is to establish the new method of small intestinal epithelial cell culture in order to make intestinal epithelial cell sheets. Cell tissue engineering and cell sheet are very unique technology for cell culture.In the field of regenerative medicine, clinical studies have already attempted to use this technology. In our study, proper cell culture condition for small intestinal cells and the method of making the cell sheet were examined. Conventional intestinal cell culture method was the three-dimensional culture. Cultured cells were unique form and called spheroid.However, this form was not appropriate for making the cell sheet. Therefore, new cell culture condition which was called the two-dimensional culture was necessary to make cell sheets. In our study, cell culture method for using rLaminin-521 coating dish and the mouse embryonic fibroblast which was co-cultured with cultured intestinal cells were the proper way to make small intestinal cell sheets. Indeed, cultured cells under two-dimensional method adhered and stretched on the dish for horizontal direction for two weeks. Gene expressions of culture cells showed that they proved to survive under that condition by confirming the stem cell markers. As to the intestinal cell sheets, the method of co-cultured with MEF enabled the making of small intestinal cell sheet. In conclusion, establishment of small intestinal cell culture in two-dimensional method and making of the intestinal cell sheet. Cell sheets will enable us to provide the efficient cell therapy from its features.

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Stem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium

Cited by 1,543 publications

References 123 publications

Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease

Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease

Genus-Specific Substitution Rate Variability among Picornaviruses

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