New cell therapy using bone marrow-derived stem cells/endothelial progenitor cells to accelerate neovascularization in healing of experimental ulcerative colitis.

Inflammatory bowel disease (IBD): ulcerative colitis (UC) and Crohn disease (CD) are characterized by recurrent inflammation and ulceration of intestinal and/or colonic mucosa and an inappropriate and delayed healing. Current therapies with, e.g., anti-TNFα antibody (infliximab) and other anti-inflammatory drugs (e.g., mesalamine) do not induce sustained remission, complete healing or prevent recurrence of UC. Although the pathogenesis of UC is not fully understood, pathologic angiogenesis has been postulated as a critical pathogenic component in UC. Recent studies demonstrated that the poor healing, chronic inflammation in colon of UC could be the result of microvascular dysfunction and endothelial barrier defect, resulting in sustained tissue hypoperfusion and ischemia in the colon. Previously, regeneration of injured endothelium and neovascularization were believed to rely solely on the migration and proliferation of neighboring endothelial cells from existing blood vessels. However, accumulating evidence shows that additional mechanisms may exist, and may be mediated by the circulating pool of bone marrow-derived endothelial progenitor cells (BMD-EPC). Furthermore, stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 have been demonstrated to play an important role in the "homing" of BMD-EPC to injured sites and neovascularization in tissue repair. Recent studies by others and us showed reduced BMD-EPC levels in the circulation of IBD patients and rats with experimental UC. However, the potential therapeutic effect of BMD-EPC on neovascularization and colonic mucosal repair in UC has not been elucidated. In this review, we discussed the possibility that impaired contribution of BMD-EPC (i.e., decreased release of BMD-EPC from bone marrow to circulation and/or blocked/impaired homing of BMD-EPC to colonic lesions) may be a critical component of mechanisms in the incomplete/delayed healing of UC, and may offer a novel form of cell therapy for IBD.