Application of Human Induced Pluripotent Stem Cell-Derived Intestinal Organoids as a Model of Epithelial Damage and Fibrosis in Inflammatory Bowel Disease.

Application of Human Induced Pluripotent Stem Cell-Derived Intestinal Organoids as a Model of Epithelial Damage and Fibrosis in Inflammatory Bowel Disease. Biol Pharm Bull. 2020;43(7):1088-1095 Authors: Onozato D, Akagawa T, Kida Y, Ogawa I, Hashita T, Iwao T, Matsunaga T Abstract Inflammatory bowel disease, which typically manifests as Crohn's disease and ulcerative colitis, is caused by the abnormal production of cytokines such as tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β. These cytokines damage intestinal epithelial cells and trigger fibrosis, respectively, for which the current in vitro models have many limitations. Therefore, we tested whether human induced pluripotent stem cell-derived intestinal organoids (HiOs) can mimic inflammatory bowel disease (IBD), and whether such a model is suitable for drug screening. HiOs were treated with TNF-α and TGF-β to construct mucosal damage and fibrosis models. TNF-α diminished the mRNA expression of intestinal epithelial cell and goblet cell markers in HiOs. TNF-α also induced epithelial cell damage and degradation of tight junctions but not in the presence of infliximab, an antibody used in the clinic to deplete TNF-α. Furthermore, permeation of the non-absorbable marker FD-4 was observed in HiOs treated with TNF-α or ethylene glycol tetraacetic acid (EGTA), but not in the presence of infliximab. In contrast, TNF-α and TGF-β i...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research

Related Links:

In this study, we examined the effects of oxytocin on the Aβ-induced impairment of synaptic plasticity in mice. To investigate the effect of oxytocin on synaptic plasticity, we prepared acute hippocampal slices for extracellular recording and assessed long-term potentiation (LTP) with perfusion of the Aβ active fragment (Aβ25-35) in the absence and presence of oxytocin. We found that oxytocin reversed the impairment of LTP induced by Aβ25-35 perfusion in the mouse hippocampus. These effects were blocked by pretreatment with the selective oxytocin receptor antagonist L-368,899. Furthermore, the tr...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The intestinal lining is an important tissue. Among its other functions, it protects the body from inflammation that can be generated by the actions of gut microbes. This barrier declines with age, and this is thought to be influential in the increased chronic inflammation observed in older people. Ways to spur greater maintenance and repair on the part of cell populations making up intestinal tissue would likely be of great benefit, given the importance of chronic inflammation as a driver of age-related disease. A strong cellular lining is essential for a healthy gut as it provides a barrier to the billions of mi...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
AbstractPreviously, the natural history of Crohn ’s disease and ulcerative colitis included significant morbidity due to limited treatment options that were not without serious side effects. Early treatment options included corticosteroids as well as mesalamine, thiopurines, and methotrexate. In 1998, monoclonal antibodies to a key inflammatory cytokine, TNFα, became available. Over the next 22 years, the field of gastroenterology has seen multiple new treatments emerging for inflammatory bowel disease (IBD) that target different aspects of the inflammatory cascade, significantly changing the therapeutic l...
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research
Background: Treatment of inflammatory bowel diseases (IBD) has tremendously improved during the last 20 years; however, a substantial fraction of patients does not respond to available therapies or lose response, and new strategies are needed.Summary: Two pharmacological principles have been successfully used for IBD treatment: inhibition of cellular signaling and interference with leukocyte trafficking. Besides tumor necrosis factor, interleukin (IL)-23 is a promising drug target, and antibodies for the combined inhibition of IL-23 and IL-12 (ustekinumab and briakinumab) or selective IL-23 inhibition (brazikumab, risankiz...
Source: Digestion - Category: Gastroenterology Source Type: research
CONCLUSION: Both, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are able to restore damaged tissue and regulate the immune system. Autologous HSCs transplantation eliminates autoreactive cells and replace them with new T-cells resulting a long-time remission. Whereas MSCs transplantation is effective therapy in one of the major complications of IBD, perianal fistulas. PMID: 32364073 [PubMed - as supplied by publisher]
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research
Abstract Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that signal using endogenous acetylcholine (ACh) and the agonist, nicotine. The nAChR signaling pathway is a central regulator of physiological homeostasis in the central and peripheral nervous systems. The receptors are expressed not only in the nervous system, but also play a pivotal role in regulation of epithelial cell growth, migration, differentiation, and inflammation processes in various mammalian non-neuronal cells. In the intestine, the Wnt signaling pathway plays a central role in the epithelium and is a principal regulato...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
In this study, by adenovirus-mediated delivery and inducible transgenic mouse models, we demonstrate the proliferation of both HCs and SCs by combined Notch1 and Myc activation in in vitro and in vivo inner ear adult mouse models. These proliferating mature SCs and HCs maintain their respective identities. Moreover, when presented with HC induction signals, reprogrammed adult SCs transdifferentiate into HC-like cells both in vitro and in vivo. Finally, our data suggest that regenerated HC-like cells likely possess functional transduction channels and are able to form connections with adult auditory neurons. Epige...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
AbstractAplastic anemia (AA) has been reported to be associated with inflammatory bowel disease (IBD), but mostly with ulcerative colitis (UC). Little is known about the associations between AA and Crohn ’s disease (CD). We aim to determine the portraits of patients with AA-CD. Among a total of 657 patients with CD registered in Xijing Hospital of Digestive Diseases IBD center from January 2008 to October 2018, the patients diagnosed with concurrent AA were reviewed. Clinical presentation, medical history, endoscopic features, response to treatment, and prognosis in this set of patients were collected. Six male patie...
Source: Annals of Hematology - Category: Hematology Source Type: research
Abstract One of the most significant challenges of inflammatory bowel disease (IBD) research is to understand how alterations in the symbiotic relationship between the genetic composition of the host and the intestinal microbiota, under impact of specific environmental factors, lead to chronic intestinal inflammation. Genome-wide association studies, followed by functional studies, have identified a role for numerous autophagy genes in IBD, especially in Crohn disease. Studies using in vitro and in vivo models, in addition to human clinical studies have revealed that autophagy is pivotal for intestinal homeostasis...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
More News: Crohn's Disease | Drugs & Pharmacology | Inflammatory Bowel Disease | Remicade | Stem Cell Therapy | Stem Cells | Ulcerative Colitis