Localized colonic stem cell transplantation enhances tissue regeneration in murine colitis

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.

Dissecting Engineered Cell Types and Enhancing Cell Fate Conversion via CellNet

“…In contrast, iHep/iEP recipient animals returned to their original weight significantly faster, showed no sign of colitis after 12 days, and instead revealed the presence of numerous GFP + donor-derived cells integrated into the colonic epithelium (Figure 6C–E). Klf-iEPs did not engraft the colon (Figure S6C), probably because mature intestinal epithelial cells cannot fulfill this role (Zhou et al, 2012). At 12 days, crypts contained a mix of GFP+ and GFP- colonocytes, as the known cell turnover would predict (Figure 6D).…”

MicroRNA 29 Targets Nuclear Factor-κB–Repressing Factor and Claudin 1 to Increase Intestinal Permeability

“…12 Testing for visceral hypersensitivity to nociceptive colonic distension was performed as described previously. 13 …”

In vivo reprogramming in inflammatory bowel disease

“…73 The source of the MSCs seems to be one of the key reasons for these opposing results. Unlike the majority of studies that use systemic (that is, intravascular) administration of stem cells, which may be associated with many side effects, Zhou et al 51 investigated if local application of adult colonic stem cells (CSCs) can increase mucosal repair. After the successful local infusion of CSCs, local inflammatory cytokines and the epithelial barrier were improved with only minimal effects on the innate immune system.…”

“…[40][41][42] However, the potential of iPS cells seems to be predominantly in regenerative medicine, and has already been proposed in cardiac repair, 43 ischemic stroke, 44 various neurological diseases 45 and diabetes. 46 Stem cellmediated therapy has also been proposed as a potential therapy for chronic diseases of a complex etiopathogenesis such as inflammatory bowel disease (IBD), although only the hematopoietic stem cells, 47,48 mesenchymal stem cells (MSCs) 49,50 and colonic stem cells 51 have been tested so far. Nevertheless, this makes the possible spectrum of iPS cells application even wider and provides a rationale for the use of iPS cells in IBD.…”