The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies

Francesco, Francesco De; Romano, Maurizio; Zarantonello, Laura; Ruffolo, Cesare; Neri, Daniele; Bassi, Nicolò; Giordano, Antonio; Zanus, Giacomo; Ferraro, Giuseppe; Cillo, Umberto

doi:10.1080/15384047.2016.1210741

Cited by 25 publications

(25 citation statements)

References 96 publications

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“…The intestinal epithelium of IBD patients undergoes repeated cycles of injury and repair in response to chronic, recurring inflammation. 47 We found decreased SIRT2 expression in the intestinal epithelium from patients with IBD. In addition, we show that SIRT2 deficiency exhibits enhanced epithelial proliferation in mice.…”

Section: Discussionmentioning

confidence: 67%

SIRT2 Contributes to the Regulation of Intestinal Cell Proliferation and Differentiation

Zhou

Rychahou

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Using complementary approaches (intestinal epithelial cell lines, intestinal organoids and SIRT2 knockout mice), we demonstrated that SIRT2, decreased in intestinal tissues from patients with inflammatory bowel diseases, contributes to the maintenance of intestinal epithelium homeostasis through regulation of Wnt-b-catenin signaling. BACKGROUND AND AIMS: Intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD). We investigated the role of Sirtuin 2 (SIRT2), a NAD-dependent protein deacetylase, in intestinal epithelial cell (IEC) proliferation and differentiation and the mechanism by which SIRT2 contributes to maintenance of intestinal cell homeostasis. METHODS: IECs were collected from SIRT2-deficient mice and patients with IBD. Expression of SIRT2, differentiation markers (mucin2, intestinal alkaline phosphatase, villin, Na,K-ATPase, and lysozyme) and Wnt target genes (EPHB2, AXIN2, and cyclin D1) was determined by western blot, real-time RT-PCR, or immunohistochemical (IHC) staining. IECs were treated with TNF or transfected with siRNA targeting SIRT2. Proliferation was determined by villus height and crypt depth, and Ki67 and cyclin D1 IHC staining. For studies using organoids, intestinal crypts were isolated. RESULTS: Increased SIRT2 expression was localized to the more differentiated region of the intestine. In contrast, SIRT2 deficiency impaired proliferation and differentiation and altered stemness in the small intestinal epithelium ex vivo and in vivo. SIRT2-deficient mice showed decreased intestinal enterocyte and goblet cell differentiation but increased the Paneth cell lineage and increased proliferation of IECs. Moreover, we found that SIRT2 inhibits Wnt/b-catenin signaling, which critically regulates IEC proliferation and differentiation. Consistent with a distinct role for SIRT2 in maintenance of gut homeostasis, intestinal mucosa from IBD patients exhibited decreased SIRT2 expression. CONCLUSION: We demonstrate that SIRT2, which is decreased in intestinal tissues from IBD patients, regulates Wnt-b-catenin signaling and is important for maintenance of IEC proliferation and differentiation.

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Section: Discussionmentioning

confidence: 67%

SIRT2 Contributes to the Regulation of Intestinal Cell Proliferation and Differentiation

Zhou

Rychahou

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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“…Due to their high therapeutic potential, ASCs are now considered an indispensable tool in regenerative medicine [61][62][63][64]. Studies have shown the successful treatment with ASCs for many disease including graft-versus-host disease [65], wound healing [66], cardiovascular [67], inflammatory bowel disease [68], diabetes mellitus [69] and several injuries including kidney and spinal cord [70], bone and craniofacial reconstruction [71,72], liver cirrhosis [73], multiple sclerosis [74]. In addition to their self-renewal ability, ASCs have the ability to differentiate into multiple lineages, including adipocytes, osteoblasts, chondrocytes, and endothelial cells [75,76].…”

Section: Is There a Role Of Adipose-derived Stem Cells (Asc) In Lipedmentioning

confidence: 99%

Lipedema: A Painful Adipose Tissue Disorder

Al-Ghadban¹,

Herbst²,

Bunnell³

2019

Adipose Tissue - An Update

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Lipedema is a painful fat disease of loose connective tissue usually misdiagnosed as lifestyle-induced obesity that affects ~10% of women of European descent as well as other populations. Lipedema is characterized by symmetric enlargement of the buttocks, hips, and legs due to increased loose connective tissue; arms are also affected in 80% of patients. Lipedema loose connective tissue is characterized by hypertrophic adipocytes, inflammatory cells, and dilated leaky blood and lymphatic vessels. Altered fluid flux through the tissue causes accumulation of fluid, protein, and other constituents in the interstitium resulting in recruitment of inflammatory cells, which in turn stimulates fibrosis and results in difficulty in weight loss. Inflammation and excess interstitial substance may also activate nerve fibers instigating the painful lipedema fat tissue. More research is needed to characterize lipedema loose connective tissue structure in depth, as well as the form and function of blood and lymphatic vessels. Understanding the pathophysiology of the disease will allow healthcare providers to diagnose the disease and develop treatments.

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“…The role of stem cells has been already intensively researched [85,86], even in inflammatory bowel diseases [87], but these potent cells have raised interest about their role or potential use in IBS.…”

Section: New Hypothesesmentioning

confidence: 99%

Inflammation as a Potential Therapeutic Target in IBS

Chira¹,

Chira²,

Dumitraşcu³

2016

Irritable Bowel Syndrome - Novel Concepts for Research and Treatment

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The pathogenesis of irritable bowel syndrome (IBS) has been intensively researched, and despite a long journey for unraveling all the structures and the pathways involved, it still remains partially obscure. Inflammation was the first to be hypothesized as a potential pathway for the pathogenesis of IBS. It remains a keystone in the complex machinery of the pathogenesis that is currently considered multifactorial. Elucidating the pathogenesis of IBS is crucial for a targeted therapy of the disease. In this chapter, we review information regarding gut inflammation in IBS, underlining some of the newest data or the cornerstones. Additionally, our aim was also to review treatment currently available and future perspectives regarding anti-inflammatory treatments for IBS. Newer techniques allow detection and research of mediators involved in inflammation, as well as their potential role to be targeted by pharmacological agents. Recent data supports not only further research of the newer agents that are currently being developed but also some of the available ones that do not have sufficient evidence. Emerging therapies that target inflammation are under evaluation, in trials. A multidrug or a multidisciplinary approach needs to be considered in some cases that fail to respond to current treatment.

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The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies

Cited by 25 publications

References 96 publications

SIRT2 Contributes to the Regulation of Intestinal Cell Proliferation and Differentiation

SIRT2 Contributes to the Regulation of Intestinal Cell Proliferation and Differentiation

Lipedema: A Painful Adipose Tissue Disorder

Inflammation as a Potential Therapeutic Target in IBS

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