Epithelial Regeneration Ability of Crohn’s Disease Assessed Using Patient-Derived Intestinal Organoids

Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn’s disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.

Download Full-text

Epithelial Regeneration Ability of Crohn's Disease Assessed Using Patient-Derived Intestinal Organoids

10.21203/rs.3.rs-509228/v1 ◽

2021 ◽

Author(s):

Chansu Lee ◽

Sung Noh Hong ◽

Eun Ran Kim ◽

Dong Kyung Chang ◽

Young-Ho Kim

Keyword(s):

Wound Healing ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Three Dimensional ◽

Regeneration Ability ◽

Necrosis Factor Alpha ◽

Epithelial Regeneration ◽

Intestinal Organoids ◽

Epithelial Cell Lines ◽

Forming Efficiency

Abstract Background: Little is known about the ability of epithelial regeneration and wound healing in patients with inflammatory bowel disease, since the ethical issue of clinical trials and the inherent limitations of tumor-derived epithelial cell lines and animal models. We evaluated the epithelial proliferation and wound healing ability of the patients with Crohn’s disease (CD) using the patient-derived intestinal organoids. Methods: Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The epithelial regeneration ability of intestinal organoids was assessed using organoid reconstitution, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU), and wound healing assays. Tumor necrosis factor-alpha (TNFa) is a major pro-inflammatory effector during the CD pathogenesis. Under the TNFa-enriched conditions, the epithelial regeneration ability of CD patient-derived organoids was compared with that of control organoids.Results: The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < .001). Long-term cultured organoids (≥ 6 passages) derived from controls and CD patients showed inseparable morphologic and cultural features. Under the TNFa-enriched conditions, organoid reconstitution assay and MTT assay revealed that the organoid reconstitution and viability of CD patient-derived organoids were significantly lower than those of control organoids (p <.05 for each). The number of EdU+ proliferative cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < .05). In the wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < .001). Conclusions: Under TNFα-enriched conditions, the wound healing ability of CD patient-derived organoids is reduced due to the reduced cell proliferation compared with that of control organoids. The epithelial regeneration ability may be impaired in patients with CD.

Download Full-text

Epithelial Regeneration Ability of Crohn's Disease Assessed Using Patient-Derived Intestinal Organoids

10.1101/2021.03.25.437111 ◽

2021 ◽

Author(s):

Chnasu Lee ◽

Sung Noh Hong ◽

Eun Ran Kim ◽

Dong Kyung Chang ◽

Young-Ho Kim

Keyword(s):

Wound Healing ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Wound Repair ◽

Ex Vivo ◽

Formation Rate ◽

Regeneration Ability ◽

Epithelial Regeneration ◽

Control Subjects ◽

Intestinal Organoids

Background: There are limitations to the utility of tumor-derived epithelial cell lines and animal models to evaluate the proliferation ability and wound repair of intestinal epithelium in the context of Crohn's disease (CD). Therefore, we aimed to study epithelial regeneration ability in CD using an intestinal organoid model. Further, since tumor necrosis factor alpha (TNFα) is a major proinflammatory effector during CD pathogenesis, we also investigated TNFα-induced alteration of regeneration ability in CD patient-derived intestinal organoids. Methods: Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from control subjects and patients with CD. The epithelial regeneration ability of intestinal organoids was assessed using organoid reconstitution, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and wound healing assays. Results: Ex vivo cultures of ileal crypt cells revealed that organoid formation rate of CD patients were reduced compared with that of control subjects (p <.001). CD patient-derived organoids sub-cultured for more than 6 passages showed stable organoid reconstitution and identical morphological features. The organoid constitution and MTT assay revealed that the viability of TNFα-treated CD patient-derived organoids were significantly lower than that of TNFα-treated control organoids (p <.05 for each). The number of EdU+ proliferative cells was significantly lower in TNFα-treated CD patient-derived organoids than in TNFα-treated control organoids (p <.05). The wound-healing ability of TNFα-treated CD patient-derived organoids was significantly lower than that of TNFα-treated control organoids (p <.001). Conclusions: The ability of proliferation and wound healing in CD-patients derived organoids is reduced, especially in TNFα-enriched condition. Our results indicated that the epithelial regenerative ability may be impaired in patients with CD under inflammatory conditions.

Download Full-text

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

Nuklearmedizin ◽

10.1055/s-0038-1629438 ◽

1988 ◽

Vol 27 (03) ◽

pp. 83-86 ◽

Cited By ~ 3

Author(s):

B. Briele ◽

F. Wolf ◽

H. J. Biersack ◽

F. F. Knapp ◽

A. Hotze

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Cell Uptake ◽

Disease Extent ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

Download Full-text

The role of epigenetic modifications for the pathogenesis of Crohn's disease

Clinical Epigenetics ◽

10.1186/s13148-021-01089-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

M. Hornschuh ◽

E. Wirthgen ◽

M. Wolfien ◽

K. P. Singh ◽

O. Wolkenhauer ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

New Biomarkers ◽

Insight Into ◽

Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

Download Full-text

An unusual case of chronic abdominal pain: an association between Celiac disease and Crohn’s disease

Oxford Medical Case Reports ◽

10.1093/omcr/omab008 ◽

2021 ◽

Vol 2021 (4) ◽

Author(s):

Leen Jamel Doya ◽

Maria Naamah ◽

Noura Karkamaz ◽

Narmin Hajo ◽

Fareeda Wasfy Bijow ◽

...

Keyword(s):

Crohn’S Disease ◽

Abdominal Pain ◽

Celiac Disease ◽

Crohn's Disease ◽

Histological Study ◽

Gastrointestinal Diseases ◽

Bowel Diseases ◽

Oral Corticosteroids ◽

History Of ◽

High Caloric Diet

ABSTRACT Inflammatory bowel diseases (IBD) and Celiac disease (CeD) are immune-mediated gastrointestinal diseases with incompletely understood etiology. Both diseases show a multifactorial origin with a complex interplay between genetic, environmental factors, and some components of the commensal microbiota. The coexistence of celiac disease with Crohn’s disease is rarely reported in the literature. Here, we report a case of a 13-year-old Syrian male who presented with a history of abdominal pain, anorexia and pallor. CeD and Crohn’s disease was documented on gastrointestinal endoscopy and histological study. The patient was treated with a gluten-free, low fiber, high caloric diet, and a course of oral corticosteroids with an improvement in growth rate and abdominal pain.

Download Full-text

Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

Mediators of Inflammation ◽

10.1155/2015/493012 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 69

Author(s):

Bruno Rafael Ramos de Mattos ◽

Maellin Pereira Gracindo Garcia ◽

Julia Bier Nogueira ◽

Lisiery Negrini Paiatto ◽

Cassia Galdino Albuquerque ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Severe Disease ◽

Biological Therapies ◽

Promising Alternative ◽

Biological Treatments ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

And Behavior

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

Download Full-text

Quality of Life Considering Patients with Chronic Inflammatory Bowel Diseases - Natural and Parenteral Nutrition

Polish Journal of Surgery ◽

10.2478/pjs-2014-0073 ◽

2014 ◽

Vol 86 (9) ◽

Cited By ~ 1

Author(s):

Aneta Raczkowska ◽

Michał Ławiński ◽

Aleksandra Gradowska ◽

Urszula Zielińska-Borkowska

Keyword(s):

Quality Of Life ◽

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Parenteral Nutrition ◽

Inflammatory Bowel Diseases ◽

Nutritional Therapy ◽

Bowel Diseases ◽

Inflammatory Bowel

AbstractOne of the elements of treatment considering inflammatory bowel diseases is nutritional therapy. The duration of the above-mentioned depends on the prevalence of such symptoms as fever, bowel move-ments, length of the functioning gastrointestinal tract, stoma and intestinal fistula presence. Nutritional therapy is an essential element of successful treatment alongside pharmacological, surgical, and biological therapy, as well as other methods. Crohn's disease and ulcerative colitis considered as chronic diseases, lead towards physical and biopsychosocial disability, being responsible for the reduction in the quality of life.was to determine the quality of life after surgical procedures in case of patients diagnosed with Crohn's disease and ulcerative colitis, subjected to natural and parenteral nutrition.The study group comprised 52 patients from the Department of Gastroen-terology, Military Medical Institute, and Department of Surgery and Clinical Nutrition, Clinical Hospital in Warsaw. The study was performed between October, 2011 and April, 2012. The World Health Organization Quality of Life Instrument - Bref (WHOQOL-BREF) questionnaire was used to deter-mine the patients’ quality of life.A lower quality of life was observed in case of patients subjected to parenteral nutrition, poor education, disease symptoms exacerbation, in the majority-rural inhabitants. The quality of life does not depend on gender, type of disease, family status, and additional medical care.

Download Full-text

A Rare Case of Gastric Crohn’s Disease Complicated by Gastric Carcinoma

POJ Clinical Case Reports ◽

10.32648/2639-3298/2/1/001 ◽

2018 ◽

pp. 1-6

Author(s):

Marwah Sami M Hussain ◽

Bandar Idrees Ali ◽

Abdullah Alzahrani

Keyword(s):

Gastric Cancer ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Inflammatory Bowel Diseases ◽

Rare Case ◽

Small Bowel Adenocarcinoma ◽

Disease Case ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Upper Gastrointestinal

Background: Inflammatory bowel diseases are strongly associated with colorectal cancer. In addition, a few cases reported with gastric and small bowel adenocarcinoma in gastroduodenal Crohn’s disease. Case report: We reported a case of a 47-Year-old female, who was referred to our surgical department and after a routine gastroscopy which revealed a lesion. Biopsy confirmed gastric well-differentiated adenocarcinoma of limited gastric Crohn’s disease, for a patient on regular anti Crohn’s medication. The patient underwent varying laparoscopic distal gastrectomy. She received adjuvant chemotherapy treatment and thereafter, she was cancer free within the period of 3- years of regular follow up. Conclusion: The only way to diagnose such lesions of a rare case of gastric cancer in a patient with Crohn’s disease is to regularly carry out upper gastrointestinal examinations. Keywords: Inflammatory bowel diseases, Crohn’s disease, Upper gastrointestinal tract Crohn’s disease, Gastric cancer

Download Full-text

Pathogenesis and management of gastrointestinal inflammation and fibrosis: from inflammatory bowel diseases to endoscopic surgery

Inflammation and Regeneration ◽

10.1186/s41232-021-00174-7 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Kentaro Iwata ◽

Yohei Mikami ◽

Motohiko Kato ◽

Naohisa Yahagi ◽

Takanori Kanai

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Tissue Repair ◽

Relevant Literature ◽

Surgical Techniques ◽

Treatment Strategies ◽

Extended Resection ◽

Bowel Diseases ◽

Technical Advances ◽

Inflammatory Bowel

AbstractGastrointestinal fibrosis is a state of accumulated biological entropy caused by a dysregulated tissue repair response. Acute or chronic inflammation in the gastrointestinal tract, including inflammatory bowel disease, particularly Crohn’s disease, induces fibrosis and strictures, which often require surgical or endoscopic intervention. Recent technical advances in endoscopic surgical techniques raise the possibility of gastrointestinal stricture after an extended resection. Compared to recent progress in controlling inflammation, our understanding of the pathogenesis of gastrointestinal fibrosis is limited, which requires the development of prevention and treatment strategies. Here, we focus on gastrointestinal fibrosis in Crohn’s disease and post-endoscopic submucosal dissection (ESD) stricture, and we review the relevant literature.

Download Full-text