Morphological transformation in esophageal submucosa by bone marrow cells: esophageal implantation under external esophageal perfusion

Accumulating clinical and experimental studies indicate that Barrett's esophagus might arise through multipotential stem cells under the stress of gastroesophageal reflux. Previously, we have presented a novel external pump perfusion rat model and demonstrated that perfusion with both acid and bile can induce severe esophagitis in 1 week with a similarly pathological change seen in humans. The aim of this study was to investigate the histological changes of esophagus after bone marrow cell engraftment with bile and acid perfusion. The external pump perfusion procedure involved implantation of a microosmotic pump for esophageal perfusion. Bone marrow cells were obtained by flushing of the femur marrow, and the cell suspension was injected between the esophageal muscular and inner mucosa layer. Histological changes were determined after 4 weeks of perfusion. Proliferating cell nuclear antigen, 8-hydroxy-deoxyguanosine, manganese superoxide dismutase, and apoptosis were measured by immunohistochemical staining and TUNEL assay, respectively. Severe esophagitis was seen in both acid and bile perfusion. Bone marrow engraftment and potentiation was seen in both the acid and bile perfusion, when compared to saline controls. Glandular-like cells in submucosa, consistent with intestinal metaplasia, confirmed by Alcin Blue-PAS staining were observed after bone marrow esophageal implantation along with bile perfusion, but not with acid perfusion and controls. Bone marrow implantation in conjunction with esophageal reflux injury contributes to abnormal histological changes consistent with early Barrett's esophageal changes. Engrafted bone marrow cells proliferate under oxidative stress conditions with bile perfusion.