Colonization and differentiation of transplanted embryonic stem cells in the irradiated intestine of mice.
Colonization and differentiation of transplanted embryonic stem cells in the irradiated intestine of mice.
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DOI：
10.1620/tjem.212.143
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发表时间：
2007-06
期刊：
影响因子：
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通讯作者：
Kohsei Kudo;Yoshinao Abe;D. Hu;H. Kijima;A. Nakane
中科院分区：
文献类型：
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作者：
Kohsei Kudo;Yoshinao Abe;D. Hu;H. Kijima;A. Nakane
放射引起的肠道损伤是腹部或骨盆癌症放射治疗的常见并发症。然而，目前对于放射性肠道损伤尚无有效的治疗方法。因此，开发新的治疗方法来治疗辐射引起的肠道损伤非常重要。在这项研究中，我们研究了胚胎干（ES）细胞是否可以直接移植到辐射损伤的肠道中，并定植并分化为肠上皮细胞。雌性裸鼠(ICR nu/nu)的肠道接受30 Gy的单剂量照射，并立即将雄性129/Sv来源的ES细胞直接注射到照射的肠壁中。移植后第13至27天切除肠道。通过聚合酶链式反应测定受辐射肠道中移植 ES 细胞的 Y 染色体 DNA。使用针对阶段特异性胚胎抗原 1、α-平滑肌肌动蛋白和细胞角蛋白 AE1/AE3 的抗体，通过组织学和免疫组织化学方法分析移植 ES 细胞在受辐射肠道中的定植和分化。在受辐射小鼠的肠道中鉴定出供体来源的细胞，并在移植后第13天观察到肠隐窝样结构。重要的是，我们观察到移植后第13天和第27天ES细胞可以在受照射的肠道粘膜下层分化为上皮细胞。这些结果表明移植的 ES 细胞可以在肠道中定植和分化。这种利用移植干细胞治疗受损肠道的新方法将是有希望的。
Radiation-induced intestinal injury is a common complication in radiotherapy for the cancer located in abdomen or pelvis. However, there is no effective treatment for radiation-induced intestinal injury now. It is therefore important to develop new treatments for radiation-induced intestinal injury. In this study, we investigated whether embryonic stem (ES) cells could be transplanted directly into the radiation-damaged intestine and could colonize and differentiate into the intestinal epithelial cells. The intestines of female nude mice (ICR nu/nu) were irradiated at a single dose of 30 Gy, and were immediately transplanted with male 129/Sv-derived ES cells into the wall of the irradiated intestine by direct injection. The intestine was removed on days 13 to 27 after transplantation. The Y-chromosome DNA of transplanted ES cells in the irradiated intestine was determined by polymerase chain reaction. Colonization and differentiation of transplanted ES cells in the irradiated intestine were analyzed by histological and immunohistochemical methods with antibodies against stage-specific embryonic antigen-1, alpha-smooth muscle actin and cytokeratin AE1/AE3. The cells of donor origin were identified in the intestine of irradiated mice, and intestinal crypt-like structures were observed on day 13 after transplantation. Importantly, we observed that ES cells could differentiate into epithelial cells in the submucosa of irradiated intestine on day 13 and 27 after transplantation. These results suggest that transplanted ES cells could colonize and differentiate in the intestinal intestine. Such a new approach for damaged intestine with transplanted stem cells would be promising.