Involvement of bone marrow-derived cells in healing of experimental colitis in rats.
Bone marrow is reported to contain hematopoietic stem cells and other adult somatic stem cells that have phenotypes of cells composing tissues other than bone marrow. To explore the implication of bone marrow-derived cells in the treatment of inflammatory bowel diseases, experimental colitis was induced in wild-type rats after transplantation of bone marrow from transgenic rats expressing green fluorescence protein (GFP). Chronic colitis was induced 21 days later using 30 mg 2,4,6-trinitrobenzenesulfonic acid (TNBS). Control rats received saline. At 28, 56, and 224 days after TNBS administration, rats were euthanized, and tissues were removed and processed for paraffin-embedded sections. Cells derived from bone marrow were identified by immunohistochemistry using anti-GFP antibody. To identify the phenotypes of the cells expressing GFP, we conducted serial-section analysis and double-staining analysis using antibodies against cytokeratin (epithelial cells) or vimentin (interstitial cells). In the present study, GFP-positive, bone marrow-derived cells occupied 37.6% and 4.25% of the colonic epithelium at 28 days and 56 days after the induction of TNBS-colitis, respectively. Also, significant amounts of mucosal and submucosal interstitial cells were derived from the bone marrow. These findings showed that a large amount of bone marrow-derived cells were involved in regeneration of the colon after experimental colitis in rats.