Abstract
Many patients suffer from chronic gastrointestinal diseases characterized by chronic inflammation, increased intestinal permeability and visceral pain in which there is no definitive treatment. Adult stem cells have recently been used in various disease states to contribute wound-healing processes. In the current study we investigated the ability of intra-colonic adult stem cells application to heal colonic inflammation in IL-10−/− mice with active colitis. The aims of this study were to determine whether intra-colonic infusion of adult colonic stem cells (CSCs) (local stem cell transplantation): (i) restores intestinal permeability; (ii) attenuates visceral hypersensitivity; (iii) heals murine colitis. IL-10−/− mice with active colitis were transplanted with adult stem cells. Mice received either a single intracolonic infusion of CSCs or colonic epithelial cells. Two weeks after transplantation, we measured visceral hypersensitivity and intestinal permeability and correlated these with histological improvement of colitis. IL-10−/− mice that received stem cell transplantation showed histopathologic evidence of recovery from colitis. Improvement in colitis as graded by pathology scores correlated with restoration of intestinal permeability and decreased visceral hypersensitivity. Intra-colonic administration of CSCs is a potential therapeutic method for treating refractory symptoms in patients with chronic gastrointestinal diseases associated with chronic inflammation and visceral hypersensitivity. This method may be safer and should have far fewer side effects than systemic stem cell administration.
Highlights
Inflammatory gastrointestinal disorders are characterized by chronic inflammation, abdominal pain, visceral hypersensitivity and diarrhoea
Colon stem cell gene expression profile further verified by quantitative real-time PCR assay and relative CT normalized with House Keeping gene (GAPDH) (Fig. S1) The self-renewal properties of colonic stem cells (CSCs) and colonic epithelial cells (CECs) were determined by Western blots and quantitative realtime PCR using different primer set (Fig. 1A)
Many patients suffer from chronic gastrointestinal diseases characterized by chronic inflammation, increased intestinal permeability, and visceral hypersensitivity and pain in which there is no definitive treatment
Summary
Inflammatory gastrointestinal disorders are characterized by chronic inflammation, abdominal pain, visceral hypersensitivity and diarrhoea. The pathophysiology of inflammatory injury to the gut is not clearly understood, but dysregulation of immunologic. Several therapeutic stem cell approaches involve the induction of circulating BMderived stem cells following systematic transplantation. Such approaches may contribute to mucosal and/or tissue repair through stimulation of regenerative responses via differentiation of the implanted stem cells. The therapeutic approaches that use stem cells such as BM-derived stem cells may contribute to mucosal repair through stimulation of regenerative responses via differentiation of BM-derived stem cells. We chose to determine if local application of adult stem cells can be beneficial during active colitis by increasing mucosal repair
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