Cultured bone marrow cell local implantation accelerates healing of ulcers in mice.

BACKGROUND

The therapeutic potential of bone marrow (BM)-derived cells in ulcers is not known. This study aimed to clarify (1) cell types that are derived from the BM which infiltrate ulcers; (2) whether BM-derived cells or gastric myofibroblasts can be used for cell transplantation to treat ulcers; and (3) the phenotypes of such transplantable cells.

METHODS

(1) Wild-type mice were transplanted with BM cells of green fluorescent protein (GFP)-transgenic mice. Acetic acid-induced gastric ulcers were produced in mice after BM transplantation. (2) BM cells and gastric myofibroblasts were isolated from GFP-transgenic mice. Bone marrow cells attached to plastic dishes were selected for expansion. Gastric ulcers were induced, and BM-derived cells, myofibroblasts, or phosphate-buffered saline were injected around ulcers. The ulcer healing process was examined macroscopically and histologically. (3) Expression of growth factors and cytokines in transplantable cells was examined by reverse transcriptase-polymerase chain reaction.

RESULTS

(1) GFP-positive cells with interstitial phenotypes were observed at the ulcerated area. (2) Ulcer healing was significantly promoted by the injection of BM-derived cells compared to controls on day 7, but not on day 3. The BM-derived cells were observed in the tissue surrounding the ulcer. However, myofibroblasts were not found. (3) The BM-derived cells expressed hepatocyte growth factor, transforming growth factor-beta(1), and other stromal factors before transplantation, and had mesenchymal phenotypes after transplantation.

CONCLUSIONS

BM-derived cells are involved in the ulcer healing. BM-derived cells, but not myofibroblasts, are locally implantable to ulcers. Thus, BM-derived cells can be transplanted to accelerate ulcer healing.