Mesenteric Adipose-derived Stromal Cells From Crohn’s Disease Patients Induce Protective Effects in Colonic Epithelial Cells and Mice With Colitis

Hoffman, Jill M.; Sideri, Aristea; Ruiz, Jonathan J.; Stavrakis, Dimitris; Shih, David Q.; Turner, Jerrold R.; Pothoulakis, Charalabos; Καραγιαννίδης, Ιορδάνης

doi:10.1016/j.jcmgh.2018.02.001

Cited by 12 publications

(12 citation statements)

References 61 publications

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“…Recently, in an interesting study, Hoffman et al [214] demonstrated that mesenteric adipose-derived stromal cells from CD patients could exert beneficial protective effects on the disease activity and severity of mice with experimental colitis. Because of the potential pathogenic role of adipose tissue and adipokines in development of IBD, some experimental studies attempt to reduce colitis severity by reducing the total or particular organ obesity.…”

Section: Year Study Type Conclusionmentioning

confidence: 99%

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

et al. 2019

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Inflammatory bowel diseases (IBDs) are a group of disorders which include ulcerative colitis and Crohn’s disease. Obesity is becoming increasingly more common among patients with inflammatory bowel disease and plays a role in the development and course of the disease. This is especially true in the case of Crohn’s disease. The recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue, also known as “creeping fat”, in pathomechanism, leading to intestinal inflammation. The involvement of altered adipocyte function and the deregulated production of adipokines, such as leptin and adiponectin, has been suggested in pathogenesis of IBD. In this review, we discuss the epidemiology and pathophysiology of obesity in IBD, the influence of a Western diet on the course of Crohn’s disease and colitis in IBD patients and animal’s models, and the potential role of adipokines in these disorders. Since altered body composition, decrease of skeletal muscle mass, and development of pathologically changed mesenteric white adipose tissue are well-known features of IBD and especially of Crohn’s disease, we discuss the possible crosstalk between adipokines and myokines released from skeletal muscle during exercise with moderate or forced intensity. The emerging role of microbiota and the antioxidative and anti-inflammatory enzymes such as intestinal alkaline phosphatase is also discussed, in order to open new avenues for the therapy against intestinal perturbations associated with IBD.

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Section: Year Study Type Conclusionmentioning

confidence: 99%

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

et al. 2019

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“…Despite different sources, MSCs have common features and behavioral traits, which not only provide cells for tissue reconstitution but also regulate inflammation and “educate” other cells to facilitate tissue repair[ 22 ]. Accumulating evidence suggests a therapeutic effect of MSCs in IBD[ 23 , 24 ] and ADSCs have been widely used because of their easy acquisition. In 2005, the first phase I clinical trial showed that 75% of fistulas were healed by ADSC therapy without any side effects[ 25 ], which opened the window to ADSC therapy for CD.…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity

Yu¹,

Zhang²,

Gu³

et al. 2020

WJG

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BACKGROUND Conventional Crohn’s disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.

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“…Mesenteric adipose tissue (MAT) hyperplasia is a hallmark of CD. Mesenteric adipose-derived stromal cells (ADSCs) synthesize and release adipokines in a disease-dependent manner and alter colonic epithelial cell signaling [201].Transmural inflammation facilitates bacterial translocation into the creeping fat, which exerts a protective effect via a localized anti-inflammatory effect, thus preventing a systemic inflammatory response in CD [202].…”

Section: Colitismentioning

confidence: 99%

Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression

Chang

Yang

2020

IJMS

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Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.

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Mesenteric Adipose-derived Stromal Cells From Crohn’s Disease Patients Induce Protective Effects in Colonic Epithelial Cells and Mice With Colitis

Cited by 12 publications

References 61 publications

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity

Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression

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