Kudo Kohsei, Abe Yoshinao, Hu Dong-Liang, Kijima Hiroshi, Nakane Akio
Department of Radiological Technology, Hirosaki University School of Health Sciences, Japan.
Tohoku J Exp Med. 2007 Jun;212(2):143-50. doi: 10.1620/tjem.212.143.
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.
放射性肠损伤是腹部或盆腔癌症放射治疗中常见的并发症。然而，目前对于放射性肠损伤尚无有效的治疗方法。因此，开发针对放射性肠损伤的新治疗方法具有重要意义。在本研究中，我们调查了胚胎干细胞（ES细胞）是否可以直接移植到受辐射损伤的肠道中，并能否定植并分化为肠上皮细胞。对雌性裸鼠（ICR nu/nu）的肠道进行单次30 Gy剂量的照射，然后通过直接注射将雄性129/Sv来源的ES细胞立即移植到受照射肠道的肠壁中。在移植后第13至27天取出肠道。通过聚合酶链反应测定受照射肠道中移植ES细胞的Y染色体DNA。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的ES细胞在受照射肠道中的定植和分化情况。在受照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细胞可在受照射肠道的黏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并分化。这种用移植干细胞治疗受损肠道的新方法具有前景。
