Abstract
Irradiation-induced esophagitis is due to ulceration of the esophagus resulting from a loss of squamous lining cells. The ulceration may result from injury of esophageal squamous stem cells. We have demonstrated that the bone marrow and esophagus contain stem cells which are transplanted following irradiation. To determine whether irradiation-induced esophagitis can be prevented by replacing the damaged esophageal squamous stem cells, we irradiated C57BL/6J mice to 30 Gy to the esophagus after which we injected them with whole bone marrow from GFP transgenic mice or esophageal progenitor cells isolated from the same donor mice. The recipient mice were then followed for the development of esophagitis. C57BL/6J mice were irradiated to 30 Gy to the upper body and injected intravenously 4 hours later with whole bone marrow cells from GFP transgenic mice ranging from 5x104 to 1x106 cells or with 1x103 esophageal progenitor cells isolated from the esophagus of GFP transgenic mice using a side population sorting technique. The mice were followed for the development of esophagitis at which time they were sacrificed and the esophagus removed and examined for GFP+ foci. Mice that did not develop esophagitis were also sacrificed, the esophagus excised, and the number of GFP+ foci determined. Mice injected with 1x106 whole bone marrow cells had an increased survival compared to mice receiving irradiation only (p = 0.0214). Mice injected with 1x103 esophageal progenitor cells also had an increased survival compared to control, irradiated mice. Examination of the esophagus revealed GFP foci, which were cytokeratin positive, located in the squamous layer of cells lining the esophagus. Injections of whole bone marrow cells or esophageal progenitor cells protect the esophagus from esophagitis by replenishing the squamous stem cells lining the lumen. Injections of whole bone marrow or marrow-derived stem cells may provide a method for repairing irradiation damage in other tissues
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