Inflammatory bowel disease: Moving toward a stem cell-based therapy.

Department of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, Bologna, Italy.
World Journal of Gastroenterology (Impact Factor: 2.37). 09/2008; 14(29):4616-26.
Source: PubMed

ABSTRACT

The incidence and prevalence of Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases (IBD), are rising in western countries. The modern hygienic lifestyle is probably at the root of a disease where, in genetically susceptible hosts, the intestinal commensal flora triggers dysregulated immune and inflammatory responses. Current therapies ranging from anti-inflammatory drugs to immunosuppressive regimens, remain inadequate. Advances in our understanding of the cell populations involved in the pathogenetic processes and recent findings on the regenerative, trophic and immunoregulatory potential of stem cells open new paths in IBD therapy. Hematopoietic and mesenchymal stem cells are catalyzing the attention of IBD investigators. This review highlights the pivotal findings for stem cell-based approaches to IBD therapy and collects the encouraging results coming in from clinical trials.

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Available from: Giacomo Lanzoni
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    • "Hence there is a pressing need for new, effective options to be identified. Evidence suggests that haematopoietic stem cell (HSC) therapy may be an effective treatment option for inflammatory gastrointestinal disorders (Singh et al., 2010; Lanzoni et al., 2008; Garcia-Bosch et al., 2010). HSCs confer benefit in experimental models of colitis and in Crohn's disease patients. "
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    ABSTRACT: Haematopoietic stem and progenitor cell (HSC) therapy may be promising for the treatment of inflammatory bowel disorders (IBDs). However, clinical success remains poor, partly explained by limited HSC recruitment following systemic delivery. The mechanisms governing HSC adhesion within inflamed colon, and whether this event can be enhanced, are not known. An immortalised HSC-like line (HPC7) was pre-treated with hydrogen peroxide (H2O2), activated platelet releasate enriched supernatant (PES) or platelet microparticles (PMPs). Subsequent adhesion was monitored using adhesion assays or in vivo ischaemia-reperfusion (IR) and colitis injured mouse colon intravitally. Integrin clustering was determined confocally and cell morphology using scanning electron microscopy. Both injuries resulted in increased HPC7 adhesion within colonic mucosal microcirculation. H2O2 and PES significantly enhanced adhesion in vitro and in the colitis, but not IR injured, colon. PMPs had no effect on adhesion. PES and PMPs induced clustering of integrins on the HPC7 surface, but did not alter their expression. Adhesion to the colon is modulated by injury but only in colitis injury can this recruitment be enhanced. The enhanced adhesion induced by PES is likely through integrin distribution changes on the HPC7 surface. Improving local HSC presence in injured colon may result in better therapeutic efficacy for treatment of IBD.
    Full-text · Article · Oct 2015 · Stem Cell Research
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    • "Attenuation of the synthesis and secretion of proinflammatory mediators is expected to be beneficial during chronic inflammatory conditions such as inflammatory bowel disease (IBD). Medical therapy for the treatment of IBD has only modest success and is associated with adverse side effects [6]. This likely contributes to the use of complementary and alternative medicine (CAM), such as herbal preparations, by as many as 50% of IBD patients [7]. "
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    ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. α-Mangostin (α-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary α-MG on murine experimental colitis and on the gut microbiota of healthy mice. Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with α-MG (0.1%). α-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with α-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in α-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed α-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC. α-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by α-MG. Our results suggest that the use of α-MG-containing supplements by patients with UC may have unintentional risk.
    Full-text · Article · Jun 2014 · Molecular Nutrition & Food Research
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    • "Despite emerging clinical evidence that these stem cells (SCs) can improve a variety of inflammatory disorders, benefits are either minor or transitory [14], [15]. This has been partially explained by low numbers of HSCs actually adhering within the local microcirculation of injured organs after injection [16]. "
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    ABSTRACT: Renal disease affects over 500 million people worldwide and is set to increase as treatment options are predominately supportive. Evidence suggests that exogenous haematopoietic stem cells (HSCs) can be of benefit but due to the rarity and poor homing of these cells, benefits are either minor or transitory. Mechanisms governing HSC recruitment to injured renal microcirculation are poorly understood; therefore this study determined (i) the adhesion molecules responsible for HSC recruitment to the injured kidney, (ii) if cytokine HSC pre-treatment can enhance their homing and (iii) the molecular mechanisms accountable for any enhancement.
    Full-text · Article · Jun 2013 · PLoS ONE
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