Experimental study for the recovery from the radiation induced intestinall damage by transplantation of ES cells and stimulation of cytokines in mice.

辐射引起的肠损伤是致命的，因为肠隐窝的再生受损。我们研究了肠道损伤恢复的两种可能方式：1）将ES细胞直接移植到受损的肠道; 2）通过细胞因子和其他物质的刺激来辅助再生能力;如表皮生长因子（EGF），褪黑激素和羟自由基清除剂-依达拉奉。1）胚胎干细胞（ES细胞）在小肠重照射区的移植在小肠局部单次照射30Gy后，将ES细胞直接注射到照射区。移植后适当时间，肉眼可见的菌落被肠道裸露区包围。显微镜下，集落由未分化细胞和分化细胞组成，构成腺泡样结构。PCR结果显示，所获得的殖民地细胞来源于ES细胞。使用免疫组织化学对菌落进行几种特殊标记物染色。结论：ES细胞在受照小肠中可增殖分化。我们尚未展示这些结果，我们现在正在准备提交给几篇论文的结果。2）EGF、褪黑激素和依达拉奉的作用在对小鼠进行全身照射后给予EGF和褪黑激素，导致小鼠死亡。它们对隐窝的殖民地形成无影响。然而，在照射前30 - 60分钟给予依达拉奉，菌落数增加。依达拉奉具有清除体内辐射产生的羟自由基的潜力。论文的一部分以日文提交和发表。

The radiation induced intestinal damage is fatal because of the impaired regeneration of intestinal crypts. We studied two possible ways of the recovery from the intestinal damage ; 1)transplantation of ES cells directly to the damaged intestine and 2)assistance of the regeneration capacity by stimulation of cytokines and other substances ; such as epidermal growth factor (EGF), melatonin and hydroxyl radical scavenger-edaravone.1)Transplantation of ES cells to the heavily irradiated area of the intestineAfter a single dose of 30Gy to a small part of intestine, ES cells were injected directly to the irradiated part. An appropriated days after transplantation, macroscopic colony was found surrounded by the denuded area of the intestine. Microscopically, colony was consisted of undifferentiated and differentiated cells constructing the acinar structures like crypt. PCR revealed that the colony cells were derived from ES cells. Colony are being stained for several special markers using immunohistochemistry. It is concluded that ES cells can proliferate and differentiated in the irradiated intestine. We have not yet presented these results and we are now preparing the results for submission to a few papers.2)The effect of EGF, melatonin and edaravoneEGF and melatonin were administered after a total body irradiation to the mouse fatally. They bad no effect on the colony formation of the crypt. However, edaravone administered 30 to 60 minutes before irradiation, the number of colony was increased. Edaravone had a potential to scavenge free hydroxyl radicals derived from radiation in vivo. A part of the paper was presented and published in Japanese.