Article

Role of mesenchymal stem cell therapy in Crohn's disease

Department of Pediatrics, Children's Mercy Hospital and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
Pediatric Research (Impact Factor: 2.84). 04/2012; 71(4 Pt 2):445-51. DOI: 10.1038/pr.2011.56
Source: PubMed

ABSTRACT Many trials of mesenchymal stem cells (MSCs) have been published in the past 5-6 y. MSCs inhibit T-cell alloreactivity in vitro by soluble factors and direct cell-to-cell contact. They are safe to infuse in humans with no acute toxicity and no ectopic tissue formation. Promising results of MSC infusion for graft-vs.-host disease and fistulizing Crohn's disease (CD) have been published. Treatment of CD requires a comprehensive treatment approach to maintain symptomatic control, improve health-related quality-of-life measures, and minimize complications from the disease. In this review, we will discuss the results of clinical trials using a novel treatment in the form of MSCs for treatment of CD and related complications. Success of these phase I, II, and III trials have set the stage for usage of this novel treatment for children with CD.

Download full-text

Full-text

Available from: Kim L Gandy, Aug 04, 2014
0 Followers
 · 
139 Views
  • Source
    • "They have been identified and isolated from multiple tissues, including adipose tissue, umbilical cord, bone marrow, muscle, and fetal liver [4]. Increasing evidence suggests that bone marrowderived mesenchymal stem cells (BMSCs) have therapeutic potential due to their immunosuppressive property in many immunological disorders, including graft-versus-host disease [5], Crohn's disease [6], and the prevention of organ transplantation rejection [7] [8]. Furthermore, many studies have demonstrated that BMSCs play a critical role in injury healing. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a G i /extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR's activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.
    Mediators of Inflammation 07/2014; 2014:565369. DOI:10.1155/2014/565369 · 3.24 Impact Factor
  • Source
    • "The above mentioned and/or other mechanisms can change the inflammatory environment to immune tolerant. It looks suitable the use of the immunosuppressive activity of MSC to the treatment of autoimmune diseases [14] [15] as well as of graft-versus-host-disease (GVHD), an important complication after allogeneic hematopoietic cells transplantation [16]. GVHD is "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mesenchymal stromal cells (MSC) are fibroblast-like cells present in different types of tissues. Their immunomodulatory potential represents a promising method for post-transplant immunotherapy in the treatment of GVHD (graft-versus-host disease) with suboptimal response to standard immunosuppression. In this study we tested influence of 1–8 month-long cryopreservation on ability of MSC to suppress activation of non-specifically stimulated lymphocytes. We did not observe any changes in proliferation capacity of MSC after thawing. Lymphocytes metabolic activity was inhibited by 30% and number of dividing cells was three times smaller in the presence of MSC. Two activation markers were studied (CD25 and CD69) to confirm preservation of functional cell integrity. Expression of CD25 antigen on CD3+CD4+ and CD3+CD4− cells was decreased in all co-cultivated samples. Level of CD69 expression on CD3+CD4+ cells was lower in samples with added MSC (10–15% on day +2) but without reaching statistical significance. The lower expression (approximately 5%) was observed also on CD4-cells. The study confirms the preservation of immunomodulatory properties of cryopreserved and re-expanded MSC. Aliquots with cryopreserved cells can represent an optimal source for a quick preparation of MSC cell product with the possibility to apply the same cells repeatedly.
    Biologicals 05/2014; DOI:10.1016/j.biologicals.2014.01.003 · 1.41 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
Show more