Molecular and clinical basis for the regeneration of human gastrointestinal epithelia

In the gastrointestinal tract, rapid renewal of the epithelium continues throughout life. Therefore, it is believed that the gastrointestinal epithelium has a prominent capacity for regeneration when tissue damage occurs. However, we face some clinical conditions in which regeneration of the gastrointestinal epithelia is severely disturbed. One example is the refractory ulcers seen in the intestine of inflammatory bowel disease patients, and a novel therapy to regenerate damaged intestinal epithelia is earnestly desired in those conditions. Little is known about the maintenance and regeneration of the intestinal epithelia, and a molecular or clinical basis for regenerative medicine is totally lacking at the moment. In this review, we discuss recent findings of the molecules regulating the proliferation and differentiation of epithelial cells. Further study of these molecules may lead to the identification and purification of intestinal stem cells that may be used as a source for transplantation in diseased patients. Endogenous stem cells also could be manipulated to correct dysregulated or prolonged regeneration in diseased patients. Alternatively, we will raise bone marrow cells as another novel source for regenerating the intestinal epithelia. Bone marrow-derived cells are the only cells of extragastrointestinal origin that are shown to contribute to the regeneration of the gastrointestinal epithelia. In bone marrow transplant recipients, donor-derived epithelial cells substantially repopulated the gastrointestinal tract during epithelial regeneration after graft-versus-host disease or ulcer formation. Utilization of these cells may also lead to a novel therapy to regenerate the damaged gastrointestinal epithelia, whether by bone marrow transplantation or by the administration of humoral factors.