Anti-fibrogenic Potential of Mesenchymal Stromal Cells in Treating Fibrosis in Crohn’s Disease

Lian, Lei; Huang, Qunsheng; Zhang, Longjuan; Qin, Huabo; He, Xiaosheng; He, Xin; Ke, Jia; Xie, Minghao; Lan, Ping

doi:10.1007/s10620-018-5082-8

Cited by 27 publications

(14 citation statements)

References 40 publications

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“…Furthermore, Mesenchymal Stromal Cells (MSCs) have been shown to possess anti-fibrogenic traits both in prophylaxis and therapy of CD-associated intestinal fibrosis induced by 2,4,5-trinitrobenzene sulphonic acid (TNBS). MSCs cause the inactivation of the TGF-β/Smad signaling pathway with a negative modulation of the inflammatory and EMT responses (Lian et al, 2018). Further potential targets for an anti-fibrotic therapy are the Rho kinases (ROCKs).…”

Section: Intestinal Fibrosismentioning

confidence: 99%

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

Gregorio

Robuffo

Spalletta³

et al. 2020

Front. Cell Dev. Biol.

107

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Fibrosis is a chronic and progressive disorder characterized by excessive deposition of extracellular matrix, which leads to scarring and loss of function of the affected organ or tissue. Indeed, the fibrotic process affects a variety of organs and tissues, with specific molecular background. However, two common hallmarks are shared: the crucial role of the transforming growth factor-beta (TGF-β) and the involvement of the inflammation process, that is essential for initiating the fibrotic degeneration. TGF-β in particular but also other cytokines regulate the most common molecular mechanism at the basis of fibrosis, the Epithelial-to-Mesenchymal Transition (EMT). EMT has been extensively studied, but not yet fully explored as a possible therapeutic target for fibrosis. A deeper understanding of the crosstalk between fibrosis and EMT may represent an opportunity for the development of a broadly effective anti-fibrotic therapy. Here we report the evidences of the relationship between EMT and multi-organ fibrosis, and the possible therapeutic approaches that may be developed by exploiting this relationship.

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Section: Intestinal Fibrosismentioning

confidence: 99%

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

Gregorio

Robuffo

Spalletta³

et al. 2020

Front. Cell Dev. Biol.

107

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“…Its clinical manifestations include abdominal pain, diarrhea, intestinal obstruction, and other enteral manifestations, such as fever and malnutrition (33). This disease is also known as localized enteritis, localized ileocolitis, segmental enteritis and granulomatous enteritis (34). The pathological features are granulomatous inflammation, fibrosis and ulceration, ulcers, paving stone changes and intestinal stenosis in the digestive tract (34).…”

Section: Discussionmentioning

confidence: 99%

“…This disease is also known as localized enteritis, localized ileocolitis, segmental enteritis and granulomatous enteritis (34). The pathological features are granulomatous inflammation, fibrosis and ulceration, ulcers, paving stone changes and intestinal stenosis in the digestive tract (34). At present, the treatment of CD is mainly comprises drugs, including glucocorticoids, salicylic acid preparations, immunosuppressive agents, antibiotics, methotrexate and biological agents (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Total flavone of Abelmoschus manihot ameliorates Crohn's disease by regulating the NF‑κB and MAPK signaling pathways

et al. 2019

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crohn's disease (cd) is a chronic relapsing form of inflammatory bowel disease, and its pathogenesis remains unknown. Total flavone of Abelmoschus manihot L. Medic (TFA), has been used as anti-inflammatory and myocardial ischemia protective drug. The present study aimed to explore the effects of TFA on CD and its underlying mechanism. We reported that TFA comprises eight flavone glycosides, including quercetin-3-O-robinobioside, gossypetin-3-O-glucoside, quercetin-3'-O-glucoside, isoquercetin, hyperoside, myricetin, gossypetin and quercetin. In vivo, TFA promoted the survival of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, decreased weight loss and increased colon length in a dose-dependent manner. Additionally, TFA notably ameliorated the inflammatory response in mice with TNBS-induced colitis as determined by histopathological analysis. In addition, the administration of TFA in mice with TNBS-induced colitis led to a significant decrease in the levels of cytokines in the sera and colon tissues; a significant decrease myeloperoxidase activity in the colon tissues was also observed. These findings may be associated with the suppression of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In vitro, TFA significantly downregulated the expression of cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. In addition, TFA suppressed LPS-induced activation of the NF-κB and MAPK signaling pathways in RAW264.7 cells. Our findings indicated that TFA could suppress the inflammatory response in mice with TNBS-induced colitis via inhibition of the NF-κB and MAPK signaling pathways. The results of the present study may improve understanding of the function of TFA and provide a novel theoretical basis for the treatment of CD.

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“…Mesenchymal stromal cells are thought to affect anti-fibrogenic activity by reducing expression of fibrotic proteins. To date, this has only been studied in mice, but could serve as a potential therapy in the future [24]. Endoscopic intralesional injection of long acting cortiscosteroids has been attempted but results are contradictory with some studies showing an earlier need for repeat dilation [25,26].…”

Section: New Investigational Therapiesmentioning

confidence: 99%

Advanced Endoscopic Techniques in the Evaluation and Treatment of Fibrostenotic Crohn's Disease

Wong¹,

Lee²

2019

obm hg

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Crohn's disease is characterized by chronic intestinal inflammation that can result in significant morbidity and loss of intestinal function over time. Many novel treatments for Crohn's disease are being developed, but a significant portion of patients still requires surgical therapy for stricturing or penetrating disease. Classically esophagogastroduodenoscopy and ileocolonoscopy have been used to diagnose patients with inflammatory bowel disease and to restage disease after starting or changing therapy. However, new endoscopic techniques are being developed to help evaluate previously inaccessible parts of the small intestine and to treat fibrostenotic complications. This review will focus on video capsule endoscopy, small bowel enteroscopy, endoscopic balloon dilation, as well as other more novel investigational endoscopic therapies for the evaluation and treatment of fibrostenotic complications.

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Anti-fibrogenic Potential of Mesenchymal Stromal Cells in Treating Fibrosis in Crohn’s Disease

Abstract: MSCs exert anti-fibrogenic activity against CD-associated fibrosis by regulating the inflammatory environment, inhibiting the TGF-beta/Smad signaling pathway and ameliorating EMT.

Cited by 27 publications

References 40 publications

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

Total flavone of Abelmoschus manihot ameliorates Crohn's disease by regulating the NF‑κB and MAPK signaling pathways

Advanced Endoscopic Techniques in the Evaluation and Treatment of Fibrostenotic Crohn's Disease

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