Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat
Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat
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DOI：
10.1007/s00535-010-0320-7
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发表时间：
2011-02
影响因子：
6.3
通讯作者：
Hiroki Tanaka;Y. Arimura;Takashi Yabana;A. Goto;M. Hosokawa;Kanna Nagaishi;K. Yamashita;Hiroyuki Yamamoto;Y. Sasaki;M. Fujimiya;K. Imai;Y. Shinomura
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文献类型：
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作者：
Hiroki Tanaka;Y. Arimura;Takashi Yabana;A. Goto;M. Hosokawa;Kanna Nagaishi;K. Yamashita;Hiroyuki Yamamoto;Y. Sasaki;M. Fujimiya;K. Imai;Y. Shinomura
背景：尽管越来越多的证据表明间充质干细胞（MSCs）参与肠组织修复，但关于MSCs在受体结肠组织中的分布、功能和命运仍然存在不确定性。因此，我们研究了移植的MSCs在DSS结肠炎修复期的作用。方法将slacz标记的大鼠间充质干细胞移植到4% DSS诱导的结肠炎大鼠体内。第6天用普通水代替DSS溶液。第9天通过临床病理和生长因子/细胞因子表达谱评估治疗效果。我们用Western blotting分析Notch信号通路，用激光共聚焦显微镜对lacz标记的MSCs进行免疫荧光表征。透射电镜（TEM）证实了间充质干细胞的体内分化。结果骨髓间充质干细胞移植可促进结肠炎的恢复，但可显著促进结肠炎的恢复。在MSC移植的结肠组织中，TgfamRNA的表达显著增加，而Notch信号被抑制。β-半乳糖苷酶阳性细胞在固有层间质中表达α-SMA、desmin和vimentin的较少。DSS暴露在体外被证明是最有效的诱导α-SMA的间充质干细胞，透射电镜显示肌源性谱系分化。结论MSCs移植可适度促进DSS结肠炎的修复。通过微环境的提示，供体来源的MSCs可能被重新编程以分化为肌源性谱系细胞。这些细胞的进一步表征被认为是应用细胞治疗炎症性肠病的基础。
BackgroundAlthough mounting evidence implicates mesenchymal stem cells (MSCs) in intestinal tissue repair, uncertainty remains concerning the distribution, function, and fate of repopulating MSCs in recipient colonic tissues. Therefore, we investigated the role of transplanted MSCs in the repair phase of DSS colitis.MethodsLacZ-labeled rat MSCs were transplanted into rats with colitis induced by 4% DSS on day 2. Regular water replaced the DSS solution on day 6. Therapeutic effect was evaluated on day 9 by clinicopathologic and growth factor/cytokine expression profiles. We analyzed the Notch signaling pathway by Western blotting and characterized immunofluorescence of lacZ-labeled MSCs with confocal laser microscopy. In vivo differentiation of MSC was confirmed by transmission electron microscopy (TEM).ResultsRecovery of colitis was modestly but significantly promoted by MSC transplantation due to proceeding cell cycle and inhibiting apoptosis in the epithelia.TgfamRNA expression increased significantly, while Notch signaling was inhibited in the colonic tissues with MSC transplantation. β-Galactosidase-positive cells, which expressed α-SMA, desmin, and vimentin, were infrequently detected in the lamina propria stroma. DSS exposure in vitro proved to be the most potent inducer for α-SMA in MSCs where TEM demonstrated myogenic lineage differentiation.ConclusionsWe found that MSCs transplantation modestly promoted the repair of DSS colitis. The donor-derived MSCs were likely reprogrammed to differentiate to myogenic lineage cells by cues from the micro milieu. Further characterization of these cells is warranted as a basis for applying cell-based therapy for inflammatory bowel disease.