Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis

González‐Rey, Elena; Anderson, Per; González, Manuel A.; Rico, Laura; Büscher, Dirk; Delgado, Mario

doi:10.1136/gut.2008.168534

Cited by 588 publications

(617 citation statements)

References 32 publications

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“…IL-1b-primed MSCs attenuate the development of DSS-Induced colitis Similar to previous reports, 27,28 we successfully induced colitis in C57BL/6 mice by oral administration of 3% DSS. The mouse colitis was characterized by sustained bloody diarrhea, weight loss, 100% mortality at day 11 ( Figure 2a, b and d), shorter and lighter colons (Figure 2c), histological changes with severe colonic transmural inflammation, increased wall thickness, localized inflammatory cell infiltration, epithelial ulceration with degeneration of crypt architecture and loss of goblet cells (Figure 2e and f).…”

Section: Resultssupporting

confidence: 81%

Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis

et al. 2012

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Mesenchymal stem cells (MSCs) have been used experimentally for treating inflammatory disorders, partly due to their immunosuppressive properties. Although interleukin-1b (IL-1b) is one of the most important inflammatory mediators, growing evidence indicates that IL-1b signaling elicits the immunosuppressive properties of MSCs. However, it remains unclear how IL-1b signaling accomplishes this activity. Here, we focus on the therapeutic efficacy of IL-1b-primed MSCs in the dextran sulfate sodium (DSS)-induced colitis model, in addition to the underlining mechanisms. We first found that IL-1b-primed MSCs, without any observable phenotype change in vitro, significantly attenuated the development of DSS-induced murine colitis. Moreover, IL-1b-primed MSCs modulated the balance of immune cells in the spleen and the mesenteric lymph nodes (MLNs) through elevating cyclooxygenase-2 (COX-2), IL-6 and IL-8 expression and influencing the polarization of peritoneal macrophages. Importantly, IL-1b-primed MSCs possessed an enhanced ability to migrate to the inflammatory site of the gut via upregulation of chemokine receptor type 4 (CXCR4) expression. In summary, IL-1b-primed MSCs have improved efficacy in treating DSS-induced colitis, which at least partly depends on their increased immunosuppressive capacities and enhanced migration ability.

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Section: Resultssupporting

confidence: 81%

Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis

et al. 2012

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“…Previous studies have demonstrated that mesenchymal stem cells (MSCs) are able to regulate the immune system, and MSCs have been used to treat a range of conditions, including acute lung injury, inflammatory bowel disease, graft versus-host reactions and ischemic heart disease (7,8). Previous attempts have been made to treat sepsis using MSCs, and MSCs have been successfully used in animals to inhibit the systemic inflammation reaction through interleukin (IL)-10, and thereby relieve the functional impairment, which is associated with sepsis and endotoxemia (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Zhou

et al. 2016

Molecular Medicine Reports

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Abstract. The present study aimed to investigate the effects of bone marrow mesenchymal stem cells (MSCs) on the cardiac function and immune system of mice with endotoxemia. The mice were divided into the following groups: Control group, endotoxemia group, lipopolysaccharide (LPS) treatment group, LPS and MSC treatment group (LPS + MSC group) and MSC group. Following treatment with LPS, the cardiac function of the mice was examined at after 2, 6 and 24 h, and on day 7. An enzyme-linked immunofluorescent assay was used to analyze the serum and the levels of cytokines in the myocardium, and western blotting was used to investigate any changes in the levels of signaling proteins associated with the myocardium. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to investigate the growth rate of the splenic cells at after 24 h and on day 7, and the humoral immune function and phagocytosis of the macrophages in the mice were also examined. The cardiac function of the mice with endotoxemia declined, although this impairment was circumvented following treatment with MSCs. The levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and IL-10 in the serum and the myocardium increased following stimulation by LPS, although these declined as a result of MSC treatment. The expression levels of Toll-like receptor 4, p65-nuclear factor-κB and phosphorylated p38 in the mouse myocardium were enhanced following stimulation by LPS, which subsequently decreased as a result of MSC treatment. Compared with the control group, the growth rate of the splenic cells, humoral immune function and the level of phagocytosis of macrophages were all increased, although these parameters declined following treatment with MSCs. Taken together, the present study revealed that the MSCs inhibited the inflammatory reaction in the mice with endotoxemia, and improved cardiac function. By contrast, the cellular and humoral immunity were depressed, and phagocytosis of the macrophages, which were enhanced following simulation with LPS, were decreased following treatment with MSCs. However, no overexpression of the anti-inflammatory factor, IL-10, was observed. The present study hypothesized that MSCs exert a bifunctional role in endotoxemia, by inhibiting inflammatory factors, including IL-1 and IL-6, and inhibiting the compensatory expression of IL-10 following LPS stimulation. This avoids the possibility of excessive inhibition of immunological function, as this results in immunosuppression, and a higher ratio of IL-10 to TNF-α is indicative of a poor prognosis in patients with sepsis.

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“…On a déjà utilisé des cellules allogéniques non appariées dans des applications cliniques; 8 des cellules xénogéniques ont même été utilisées avec succès dans des modèles précliniques immunocompétents. 9 On a attribué cette capacité remarquable des CSM à échapper à la détection du système immunitaire du receveur à l'absence d'un complexe majeur d'histocompatibilité de classe II et de molécules co-stimulantes nécessaires à la reconnaissance des cellules hôtes T CD4?. 10 Le statut 'immunoprivilégié' des CSM est important d'un point de vue clinique.…”

Section: Que Sont Les Cellules Stromales Mésenchymateuses?unclassified

“…Mismatched allogeneic cells have been used clinically, 8 and even xenogeneic cells have been used successfully in immunocompetent preclinical models. 9 This remarkable ability of MSCs to evade detection by the recipient's immune system has been attributed to the lack of major histocompatibility complex class II and co-stimulatory molecules necessary for host CD4? T cell recognition.…”

mentioning

confidence: 99%

Adult stem cells: potential implications for perioperative medicine

Lalu

Barron

Stewart

et al. 2014

Can J Anesth/J Can Anesth

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Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis

Abstract: hASCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for IBD and sepsis.

Cited by 588 publications

References 32 publications

Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis

Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis

Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia

Adult stem cells: potential implications for perioperative medicine

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