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，因为它损害了肠隐窝的再生。我们研究了两种可能的肠道损伤恢复方式；1)将胚胎干细胞直接移植到受损的肠道，2)通过刺激细胞因子和其他物质来辅助再生能力；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)胚胎干细胞移植至小肠重辐照区一小部分经30Gy单次剂量照射后，将胚胎干细胞直接注射至受辐照部位。移植后约1天，可见肉眼可见的菌落被肠壁剥落区包围。显微镜下，菌落由未分化细胞和分化细胞组成，形成隐窝等腺泡结构。PCR结果显示，该集落细胞来源于胚胎干细胞。利用免疫组织化学对菌落进行几种特殊标记物染色。由此可见，胚胎干细胞在辐照后的肠内具有增殖和分化的能力。我们还没有提交这些结果，我们正在准备将结果提交给几篇论文。2) EGF、褪黑素和依达拉奉在小鼠全身致命照射后给予EGF和褪黑素的作用。它们对地穴的蜂群形成没有影响。而在照射前30 ~ 60分钟给予依达拉奉，菌落数量增加。依达拉奉在体内有清除辐射产生的游离羟基自由基的潜力。论文的一部分以日文发表。

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.