Okamoto Ryuichi, Watanabe Mamoru
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
J Gastroenterol. 2004 Jan;39(1):1-6. doi: 10.1007/s00535-003-1259-8.
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.
在胃肠道中，上皮细胞的快速更新贯穿一生。因此，人们认为当组织受损时，胃肠道上皮具有显著的再生能力。然而，我们面临一些临床情况，其中胃肠道上皮的再生受到严重干扰。一个例子是炎症性肠病患者肠道中出现的难治性溃疡，在这些情况下，迫切需要一种新的疗法来再生受损的肠道上皮。关于肠道上皮的维持和再生知之甚少，目前完全缺乏再生医学的分子或临床基础。在这篇综述中，我们讨论了调节上皮细胞增殖和分化的分子的最新研究结果。对这些分子的进一步研究可能会导致鉴定和纯化肠道干细胞，这些干细胞可作为患病患者移植的来源。内源性干细胞也可以被操纵来纠正患病患者中失调或延长的再生。或者，我们将提出骨髓细胞作为再生肠道上皮的另一种新来源。骨髓来源的细胞是唯一显示出有助于胃肠道上皮再生的胃肠道外源性细胞。在骨髓移植受者中，供体来源的上皮细胞在移植物抗宿主病或溃疡形成后的上皮再生过程中大量重新填充了胃肠道。利用这些细胞也可能导致一种新的疗法来再生受损的胃肠道上皮，无论是通过骨髓移植还是通过给予体液因子。
