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


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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    • "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.
    Molecular Nutrition & Food Research 06/2014; 58(6). DOI:10.1002/mnfr.201300771 · 4.60 Impact Factor
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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. Adherent and free-flowing HSCs were determined in an intravital murine model of renal ischaemia-reperfusion injury. Some HSCs and animals were pre-treated prior to HSC infusion with function blocking antibodies, hyaluronidase or cytokines. Changes in surface expression and clustering of HSC adhesion molecules were determined using flow cytometry and confocal microscopy. HSC adhesion to endothelial counter-ligands (VCAM-1, hyaluronan) was determined using static adhesion assays in vitro. CD49d, CD44, VCAM-1 and hyaluronan governed HSC adhesion to the IR-injured kidney. Both KC and SDF-1α pre-treatment strategies significantly increased HSC adhesion within injured kidney, whilst SDF-1α also increased numbers continuing to circulate. SDF-1α and KC did not increase CD49d or CD44 expression but increased HSC adhesion to VCAM-1 and hyaluronan respectively. SDF-1α increased CD49d surface clustering, as well as HSC deformability. Increasing HSC adhesive capacity for its endothelial counter-ligands, potentially through surface clustering, may explain their enhanced renal retention in vivo. Furthermore, increasing HSC deformability through SDF-1α treatment could explain the prolonged systemic circulation; the HSC can therefore continue to survey the damaged tissue instead of becoming entrapped within non-injured sites. Therefore manipulating these mechanisms of HSC recruitment outlined may improve the clinical outcome of cellular therapies for kidney disease.
    PLoS ONE 06/2013; 8(6):e66489. DOI:10.1371/journal.pone.0066489 · 3.23 Impact Factor
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    • "Consequently, researchers have been eagerly seeking alternative methods of establishing lifelong tolerance while minimizing toxicity. Studies have reported numerous active clinical trials in which mesenchymal stem cells (MSCs) are used in the treatment of inflammatory diseases, such as graft-versus-host disease (GVHD) [12] [13], Crohn's disease [14] [15], ulcerative colitis [16], multiple sclerosis [17] [18], and systemic lupus erythematosus [19] [20]. Herein, we focus on the immunomodulatory effects of MSCs, provide a snapshot of the results from current in vitro and in vivo studies, and discuss future prospects in which these procedures can be made widely available in VCA. "
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    ABSTRACT: Vascularized composite allotransplantations (VCAs) are not routinely performed for tissue reconstruction because of the potentially harmful adverse effects associated with lifelong administration of immunosuppressive agents. Researchers have been eagerly seeking alternative methods that circumvent the long-term use of immunosuppressants. Mesenchymal stem cells (MSCs) show promise as an immunomodulatory therapeutic agent and are currently being tested in preclinical and clinical settings as therapies for autoimmune disorders or transplant rejection. The mechanisms by which MSCs modulate the immune response are still under thorough investigation, but these most likely involve expression of local factors influencing T-cell regulation, modulation of cytokine expression (e.g., IL-10, TGF-β, TNF-α, INF-γ, etc.), and interactions with dendritic or antigen presenting cells. In this paper, we summarize the current understanding of immunomodulation achieved by MSC therapies and introduce a possible outline for future clinical applications in VCA.
    Clinical and Developmental Immunology 11/2012; 2012:854846. DOI:10.1155/2012/854846 · 2.93 Impact Factor
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