脂肪源性间充质干细胞条件培养基和肠系膜缺血再灌注中肠干细胞的增殖
Adipose-derived mesenchymal stem cell-conditioned medium and proliferation of intestinal stem cells in mesenteric ischemia and reperfusion.
摘要(中文译文)
肠系膜缺血即使在血流再通后也常导致肠坏死，即再灌注损伤，目前尚无经验证的有效疗法可用于保护肠道。脂肪来源间充质干细胞条件培养基（MSC-CM）作为一种组织工程与再生治疗方法，被认为可能是器官损伤急性期治疗的可行手段。本研究旨在阐明MSC-CM对缺血和再灌注所致肠组织损伤的治疗作用。小鼠被分为三组，分别接受60分钟肠系膜动脉阻断（缺血组）、阻断60分钟后复灌60分钟（再灌注组），或经眶后静脉注射200 µL MSC-CM后进行相同时长的缺血-再灌注（MSC-CM组）。取远端回肠，采用caspase-3和肠道干细胞特异性标志物LGR5进行免疫荧光染色，以评估损伤部位及MSC-CM所保护的细胞类型。此外，采用定量聚合酶链反应检测LGR5、Notch1、Jagged 1、Hes1、DLL1、DLL3和DLL4的mRNA表达。缺血广泛损伤上皮层，再灌注诱导上皮层细胞凋亡。给予MSC-CM与隐窝基底部细胞的保存相关，双免疫荧光染色鉴定这些细胞为肠道干细胞。MSC-CM组的LGR5表达显著高于再灌注组和缺血组。同样，MSC-CM组表现出更高的Notch1和Jag1表达，而再灌注组显示更高的Notch1表达。总之，MSC-CM的使用与绒毛隐窝处肠道干细胞的保存以及更高的Notch1和Jag1表达相关。
Abstract
Mesenteric ischemia frequently causes bowel necrosis even after recirculation, known as reperfusion injury, and no effective therapy has been validated for preserving the intestine. Adipose-derived mesenchymal stem cell-conditioned medium (MSC-CM), a tissue engineering and regenerative therapy, has been suggested as a feasible acute-phase treatment for organ damages. This study aimed to elucidate the therapeutic effects of MSC-CM on intestinal tissue injuries by ischemia and reperfusion. Mice were categorized into three groups that underwent either 60-min mesenteric artery occlusion (ischemia group), 60-min reperfusion following 60-min occlusion (reperfusion group), or ischemia-reperfusion with the same duration following intravenous administration of 200-µL MSC-CM by retroorbital injection (MSC-CM group). The distal ileum was harvested, and immunofluorescence staining with caspase-3 and LGR5, an intestinal stem cell-specific marker, was performed for evaluating the injury location and type of cells protected by MSC-CM. Moreover, LGR5, Notch1, Jagged 1, Hes1, DLL1, DLL3, and DLL4 mRNA expressions were measured using quantitative polymerase chain reaction. Ischemia extensively damaged the epithelial layer, and reperfusion-induced cellular apoptosis at the epithelial layer. MSC-CM administration was associated with preservation of cells at the crypt base, which were identified as intestinal stem cells using double-immunofluorescence staining. The MSC-CM group demonstrated significantly higher LGR5 expression than the reperfusion and ischemia groups. Similarly, the MSC-CM group exhibited higher Notch1 and Jag1 expressions, whereas the reperfusion group showed a higher Notch1 expression. In conclusion, MSC-CM use was associated with preservation of the intestinal stem cells at the crypt of villi and higher Notch1 and Jag1 expressions.
如何引用
AMA
Ryo Yamamoto, Sayuri Suzuki, Koichiro Homma, Katsuya Maeshima, Yasuo Komura, Junichi Sasaki. Adipose-derived mesenchymal stem cell-conditioned medium and proliferation of intestinal stem cells in mesenteric ischemia and reperfusion.. Scientific reports. 2026; doi:10.1038/s41598-026-60593-9.
APA
Ryo Yamamoto, Sayuri Suzuki, Koichiro Homma, Katsuya Maeshima, Yasuo Komura, Junichi Sasaki (2026). Adipose-derived mesenchymal stem cell-conditioned medium and proliferation of intestinal stem cells in mesenteric ischemia and reperfusion.. Scientific reports. https://doi.org/10.1038/s41598-026-60593-9
GB/T 7714
Ryo Yamamoto, Sayuri Suzuki, Koichiro Homma, Katsuya Maeshima, Yasuo Komura, Junichi Sasaki. Adipose-derived mesenchymal stem cell-conditioned medium and proliferation of intestinal stem cells in mesenteric ischemia and reperfusion.[J]. Scientific reports, 2026 doi:10.1038/s41598-026-60593-9.
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