Novel Cell-Based Therapeutic Strategy for Ischemic Colitis with Use of Bone Marrow–Derived Mononuclear Cells in Rats

Abstract

Ischemic colitis is a common disorder of the large bowel. In the clinical setting, some patients suffer refractory ischemic colitis regardless of conventional treatment. Meanwhile, bone marrow-derived mononuclear cells are known to accelerate neovascularization. The purpose of this study was to verify the effects of bone marrow-derived mononuclear cells on ischemic colitis in rats. An ischemic colitis model was established by partial obstruction of the rectum and interruption of the marginal vessel in the immunodeficient rat. Bone marrow-derived mononuclear cells from a Wistar rat were injected into the ischemic area one day later than the ischemia (Group MNC). As a control, phosphate-buffered saline was injected in the same manner (Group PBS). Seven days after cell transplantation, each rat was evaluated for histology and colic motility. Compared with Group PBS scores, the Group MNC macroscopic and microscopic colitis severity scores were significantly reduced. Moreover, the density of the capillary and myenteric plexus was significantly higher in Group MNC than in Group PBS (9.55 +/- 0.74 vs. 4.61 +/- 0.22, respectively, P < 0.01; and 8.57 +/- 0.41 vs. 5.93 +/- 0.31, respectively, P < 0.02). The whole-gut transit time was significantly shorter in Group MNC compared with Group PBS (472.7 +/- 17.6 vs. 584.8 +/- 24.0 minutes, respectively, P < 0.01). Transplanted cells were detected in all layers of the intestinal wall; however, these cells did not differentiate into vascular or neural cells. These results suggest that transplantation of bone marrow-derived mononuclear cells might enhance not only tissue regeneration and angiogenesis but also neurogenesis. Transplantation of bone marrow-derived mononuclear cells may be a useful therapeutic strategy for ischemic colitis.