Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model
Effects of Human Adipose Tissue-Derived and Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in a Dextran Sulfate Sodium-Induced Mouse Model
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DOI：
10.1089/biores.2019.0022
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发表时间：
2019-11-01
影响因子：
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通讯作者：
Terai, Shuji
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文献类型：
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作者：
Ikarashi, Shunzo;Tsuchiya, Atsunori;Terai, Shuji
间充质干细胞（MSC）可以从医疗废物中获得。MSC易于扩增，具有多种功能，包括抗炎作用。我们评估了人脂肪组织来源的MSC（AD-MSC）和脐带组织来源的MSC（UC-MSC）在葡聚糖硫酸钠（DSS）诱导的小鼠模型中的作用。将人AD-MSC和UC-MSC（1 × 10（6）个细胞）静脉内注射到7天DSS诱导的结肠炎模型中。评价了细胞来源、注射时间和从MSC培养物获得的上清液的治疗效果。我们还分析了间充质干细胞、组织和肠道植物群中信使RNA（mRNA）的表达。发现AD-MSC和UC-MSC在小鼠模型中第3天注射时显示出强烈的抗炎作用。第11天，结肠组织中炎症因子的mRNA水平在第3天注射MSC后显著降低。MSC培养上清液降低了肿瘤坏死因子（TNF）-α的mRNA水平，但与MSC细胞注射相比，治疗效果降低。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-κ B和T细胞受体信号传导途径的变化。另外的分析显示，在加入来自DSS结肠炎小鼠的血清后，MSC中的几个因子，包括染色体10开放阅读框54、斯钙素-1和TNF受体超家族成员11 b增加。AD-MSCs和UC-MSCs均能维持肠道植物群的平衡。总之，AD-MSCs和UC-MSCs在早期细胞注射后显示出抗炎症的治疗效果，同时维持肠道植物群。虽然上清液显示出治疗效果，但细胞注射对炎症更有效。
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 x 10(6) 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)-alpha, 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-alpha/nuclear factor-kappa B 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.