Human Small Intestinal Epithelial Cells Differentiated from Adult Intestinal Stem Cells as a Novel System for Predicting Oral Drug Absorption in Humans

2014 ◽  
Vol 42 (11) ◽  
pp. 1947-1954 ◽  
Author(s):  
Toru Takenaka ◽  
Naomoto Harada ◽  
Jiro Kuze ◽  
Masato Chiba ◽  
Takahiro Iwao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Drug Absorption ◽  
Intestinal Epithelial Cells ◽  
Intestinal Stem Cells ◽  
Oral Drug ◽  
Intestinal Epithelial ◽  
Oral Drug Absorption ◽  
Small Intestinal

Application of human IPSC-derived intestinal epithelial cells for evaluating oral drug absorption

2017 ◽  
Vol 32 (1) ◽  
pp. S70-S71
Author(s):  
Takanori Akazawa ◽  
Shinpei Yoshida ◽  
Koji Takahashi ◽  
Naoki Kusu ◽  
Yoshitaka Yamaguchi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Drug Absorption ◽  
Intestinal Epithelial Cells ◽  
Oral Drug ◽  
Intestinal Epithelial ◽  
Oral Drug Absorption ◽  
Human Ipsc

Differentiation and Proliferation of Intestinal Stem Cells and its Underlying Regulated Mechanisms during Weaning

2019 ◽  
Vol 20 (7) ◽  
pp. 690-695
Author(s):  
Xi Chen ◽  
Zehong Yang ◽  
Huiling Hu ◽  
Wentao Duan ◽  
Aiping Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Goblet Cells ◽  
Intestinal Stem Cells ◽  
Stressful Event ◽  
Intestinal Epithelial ◽  
Gut Barrier Function ◽  
Weaning Stress ◽  
Differentiation And Proliferation

Weaning is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Many studies have reported the changes that happened in the gut of various mammals such as pigs and rats after weaning. These findings suggest that the development of intestinal tract mainly is affected at the time of weaning through interfering in the differentiation and proliferation of intestinal stem cells. Weaning stress stimulates the rapid differentiation and proliferation of intestinal stem cells in order to adjust to changes caused by weaning, which are mainly manifested as deeper crypt depth and decreased intestine villus height. However, the accelerated cellular process may lead to an increase in the proportion of immature intestinal epithelial cells and goblet cells, which affect intestinal permeability and reduce the gut-barrier function against toxins and pathogens. This review briefly describes the effects coforticotrophin-releasing factor (CRF), epidermal growth factor (EGF) and polyamines on the differentiation and proliferation of intestinal stem cells after weaning and discusses its possible underlying regulatory mechanisms. Firstly, weaning stress activates CRF to binds its receptors, which induces proinflammatory responses and promote rapid differentiation and proliferation of intestinal stem cells to a larger fraction of immature intestinal epithelial cells and goblet cells. Secondly, the lack of EGF after weaning inhibits the expression of goblet cell maturation factors and makes it difficult for goblet cells and intestinal epithelial cells to mature. Finally, diet and endogenous synthesis lead to excessive polyamines in the intestine, which promote the proliferation of intestinal stem cells by regulating the expression of human antigen R (HuR) and other related genes at the time of weaning.

scholarly journals Fluorescent labelling of intestinal epithelial cells reveals independent long-lived intestinal stem cells in a crypt

2014 ◽  
Vol 454 (4) ◽  
pp. 493-499 ◽  
Author(s):  
Nobukatsu Horita ◽  
Kiichiro Tsuchiya ◽  
Ryohei Hayashi ◽  
Keita Fukushima ◽  
Shuji Hibiya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Fluorescent Labelling

scholarly journals Arid1a is essential for intestinal stem cells through Sox9 regulation

2019 ◽  
Vol 116 (5) ◽  
pp. 1704-1713 ◽  
Author(s):  
Yukiko Hiramatsu ◽  
Akihisa Fukuda ◽  
Satoshi Ogawa ◽  
Norihiro Goto ◽  
Kozo Ikuta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Functional Role ◽  
Molecular Mechanisms ◽  
Intestinal Epithelial Cells ◽  
Lineage Tracing ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Intestinal Homeostasis ◽  
Self Renewal

Inactivating mutations of Arid1a, a subunit of the Switch/sucrose nonfermentable chromatin remodeling complex, have been reported in multiple human cancers. Intestinal deletion of Arid1a has been reported to induce colorectal cancer in mice; however, its functional role in intestinal homeostasis remains unclear. We investigated the functional role of Arid1a in intestinal homeostasis in mice. We found that intestinal deletion of Arid1a results in loss of intestinal stem cells (ISCs), decreased Paneth and goblet cells, disorganized crypt-villous structures, and increased apoptosis in adult mice. Spheroids did not develop from intestinal epithelial cells deficient for Arid1a. Lineage-tracing experiments revealed that Arid1a deletion in Lgr5+ ISCs leads to impaired self-renewal of Lgr5+ ISCs but does not perturb intestinal homeostasis. The Wnt signaling pathway, including Wnt agonists, receptors, and target genes, was strikingly down-regulated in Arid1a-deficient intestines. We found that Arid1a directly binds to the Sox9 promoter to support its expression. Remarkably, overexpression of Sox9 in intestinal epithelial cells abrogated the above phenotypes, although Sox9 overexpression in intestinal epithelial cells did not restore the expression levels of Wnt agonist and receptor genes. Furthermore, Sox9 overexpression permitted development of spheroids from Arid1a-deficient intestinal epithelial cells. In addition, deletion of Arid1a concomitant with Sox9 overexpression in Lgr5+ ISCs restores self-renewal in Arid1a-deleted Lgr5+ ISCs. These results indicate that Arid1a is indispensable for the maintenance of ISCs and intestinal homeostasis in mice. Mechanistically, this is mainly mediated by Sox9. Our data provide insights into the molecular mechanisms underlying maintenance of ISCs and intestinal homeostasis.

scholarly journals Human Primary Intestinal Epithelial Cells as an ImprovedIn VitroModel for Cryptosporidium parvum Infection

2013 ◽  
Vol 81 (6) ◽  
pp. 1996-2001 ◽  
Author(s):  
Alejandro Castellanos-Gonzalez ◽  
Miguel M. Cabada ◽  
Joan Nichols ◽  
Guillermo Gomez ◽  
A. Clinton White
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Host Parasite Interactions ◽  
Intestinal Pathogens ◽  
Novel Method ◽  
Host Parasite

ABSTRACTThe study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolongedin vitrocultivation of PECs that can be used to studyCryptosporidiuminfection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected withCryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells supportCryptosporidiumbetter than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involvingCryptosporidiumand other intestinal pathogens.

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