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Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model

机译:人脂肪组织和脐带组织间充质干细胞在葡聚糖硫酸钠诱导小鼠模型中的作用

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Mesenchymal stem cells (MSCs) can be acquired from medical waste. MSCs are easily expanded and have multiple functions, including anti-inflammatory effects. We evaluated the effects of human adipose tissue-derived MSCs (AD-MSCs) and umbilical cord tissue-derived MSCs (UC-MSCs) in a dextran sulfate sodium (DSS)-induced mouse model. Human AD-MSCs and UC-MSCs (1?×?106 cells) were injected intravenously into a 7-day DSS-induced colitis model. The therapeutic effects of cell origin, injection timing, and supernatants obtained from MSC cultures were evaluated. We also analyzed messenger RNA (mRNA) expression in MSCs, tissues, and intestinal flora. AD-MSCs and UC-MSCs were found to show strong anti-inflammatory effects when injected on day 3 in a mouse model. On day 11, the mRNA levels of inflammatory factors in colon tissues were significantly decreased after injection of MSCs on day 3. Supernatants from MSCs culture decreased mRNA levels of tumor necrosis factor ( Tnf )-α, but had reduced therapeutic effects compared with MSC cell injection. RNA sequencing using colon tissues obtained the day after cell injection revealed changes in the TNF-αuclear factor-κB and T cell receptor signaling pathways. Additional analyses showed that several factors, including chromosome 10 open reading frame 54, stanniocalcin-1, and TNF receptor superfamily member 11b were increased in MSCs after adding serum from DSS colitis mice. Furthermore, both AD-MSCs and UC-MSCs maintained the balance of intestinal flora. In conclusion, AD-MSCs and UC-MSCs showed therapeutic effects against inflammation after early cell injection while maintaining the intestinal flora. Although supernatants showed therapeutic effects, cell injection was more effective against inflammation.
机译:间充质干细胞(MSCs)可以从医疗废物中获取。 MSC易于扩增并具有多种功能,包括抗炎作用。我们评估了人脂肪组织衍生的MSC(AD-MSC)和脐带组织衍生的MSC(UC-MSC)在右旋糖酐硫酸钠(DSS)诱导的小鼠模型中的作用。将人AD-MSC和UC-MSC(1××106个细胞)静脉内注射到7天DSS诱导的结肠炎模型中。评价了来自MSC培养物的细胞来源,注射时间和上清液的治疗效果。我们还分析了MSC,组织和肠道菌群中的信使RNA(mRNA)表达。当在小鼠模型中第3天注射时,发现AD-MSC和UC-MSC显示出强的抗炎作用。在第11天,在第3天注射MSCs后,结肠组织中炎性因子的mRNA水平显着降低。从MSCs培养物上清液降低了肿瘤坏死因子(Tnf)-α的mRNA水平,但与MSC细胞相比具有降低的治疗作用注射。使用细胞注射后第二天获得的结肠组织进行的RNA测序揭示了TNF-α/核因子-κB和T细胞受体信号通路的变化。进一步的分析表明,从DSS结肠炎小鼠中添加血清后,MSC中的一些因子(包括10号染色体的开放阅读框54,斯坦尼钙蛋白-1和TNF受体超家族成员11b)增加。此外,AD-MSC和UC-MSC均维持肠道菌群的平衡。总之,AD-MSC和UC-MSC在早期细胞注射后显示出对炎症的治疗效果,同时保持了肠道菌群。尽管上清液显示出治疗效果,但细胞注射更有效地抵抗炎症。

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