The transdifferentiation of bone-marrow-derived cells in colonic mucosal regeneration after dextran-sulfate-sodium-induced colitis in mice
The transdifferentiation of bone-marrow-derived cells in colonic mucosal regeneration after dextran-sulfate-sodium-induced colitis in mice
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DOI：
10.1159/000104148
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发表时间：
2007-01-01
期刊：
影响因子：
3.1
通讯作者：
Kawano, Sunao
中科院分区：
文献类型：
--
作者：
Hayashi, Yujiro;Tsuji, Shingo;Kawano, Sunao
骨髓源性细胞 (BMDC) 转分化为各种类型的胃肠道细胞。然而，BMDC 在肠道再生中的精确转分化仍存在争议。在这项研究中，我们检查了 BMDC 在受损结肠上皮再生中的转分化。通过雄性绿色荧光蛋白转基因小鼠供体的骨髓移植来拯救受到致命辐射的野生型雌性小鼠（C57BL/6）。骨髓移植后第28天，通过在饮用水中添加3％右旋糖酐硫酸钠(DSS)连续5天来诱发慢性结肠炎。 DSS 给药后第 25 天处死小鼠。通过共聚焦显微镜和荧光免疫组织化学检查 BMDC 表型。波形蛋白阳性的结肠间质细胞中经常观察到BMDC，这些细胞也表达α-平滑肌肌动蛋白并具有纺锤样形态，但不表达白细胞共同抗原。绿色荧光蛋白阳性细胞很少或较少见于 Ki-67 阳性增殖细胞、细胞角蛋白阳性上皮细胞或 CD31 阳性内皮细胞。 BMDC经常转分化为上皮下肌成纤维细胞和成纤维细胞，并且在实验性结肠炎愈合后通常继续驻留在结肠上皮下层中。总之，我们的数据表明 BMDC 的命运，可能参与 DSS 诱导的结肠炎后结肠的愈合过程。我们的数据显示，结肠炎愈合后，BMDC 有助于结肠间质细胞的形成。了解 BMDC 的命运对于 BMDC 的干细胞治疗可能很重要。版权所有 (c) 2007 S. Karger AG，巴塞尔。
Bone-marrow-derived cells ( BMDCs) transdifferentiate into various types of gastrointestinal cells. The precise transdifferentiation of BMDCs in gut regeneration, however, is controversial. In this study, we examined the transdifferentiation of BMDCs in the regeneration of damaged colonic epithelia. Lethally irradiated wild-type female mice ( C57BL/6) were rescued by bone marrow transplantation from male green fluorescent protein transgenic mouse donors. Chronic colitis was induced by administering 3% dextran sulfate sodium ( DSS) in the drinking water for 5 days on day 28 after the bone marrow transplantation. The mice were killed on day 25 after DSS administration. BMDC phenotypes were examined by confocal microscopy and fluorescence immunohistochemistry. BMDCs were frequently observed in the vimentin-positive colonic interstitial cells, which also expressed alpha-smooth muscle actin and had a spindle-like morphology, but did not express leukocyte common antigen. Green-fluorescent-protein-positive cells were rarely or less frequently found in Ki-67-positive proliferating cells, cyto-keratin-positive epithelial cells, or CD31-positive endothelial cells. BMDCs frequently transdifferentiated into subepithelial myofibroblasts and fibroblasts, and often continued to reside in the colonic subepithelia after the experimental colitis had healed. In conclusion, our data indicate the fate of BMDCs, which might be involved in the healing process of the colon after DSS-induced colitis. Our data show that BMDCs contribute to colonic interstitial cells after the colitis has healed. Understanding the fate of BMDCs may be important for stem cell therapy by BMDCs. Copyright (c) 2007 S. Karger AG, Basel.