Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors
Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors
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DOI：
10.1007/s00535-013-0901-3
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发表时间：
2014-02-01
影响因子：
6.3
通讯作者：
Shinomura, Yasuhisa
中科院分区：
文献类型：
--
作者：
Watanabe, Shuhei;Arimura, Yoshiaki;Shinomura, Yasuhisa
虽然越来越多的证据表明间充质干细胞（MSC）在肠组织修复，仍然存在争议的移植，增殖和分化的MSC在受体组织中重新填充。因此，我们研究了MSC在实验性结肠炎中的旁分泌和/或内分泌作用，分析了MSC条件培养液（MSC-CM）对葡聚糖硫酸钠（DSS）或2，4，6-三硝基苯磺酸（TNBS）诱导的结肠炎的治疗作用。我们研究了MSC-CM对离体固有层/肠系膜淋巴细胞、巨噬细胞系和混合淋巴细胞反应中上皮细胞活力、迁移率、细胞周期和细胞因子产生的影响。探索了治疗结肠炎的最佳方案。采用WNT信号通路聚合酶链反应阵列、炎性细胞因子抗体阵列和液相色谱-串联质谱分析MSC-CM的含量，不依赖于全身给药途径，MSC-CM浓缩物对TNBS诱导的结肠炎的诱导期和DSS诱导的结肠炎的恢复期有效。低氧似乎是通过激活大鼠小肠上皮细胞IEC-6中的PI 3 K-Akt通路来评估细胞运动性和活力的最佳预处理因素之一。因此，缺氧对MSC-CM的内容物产生了深远的影响，MSC-CM包括参与每个伤口愈合过程的多效肠道营养因子，包括抗炎、增殖和组织重塑阶段，迫切需要鉴定和优化MSC-CM中潜在的肠道营养因子，以形成新药发现和优化炎症性肠病的细胞治疗的基础。
Although mounting evidence implicates mesenchymal stem cells (MSCs) in intestinal tissue repair, controversy remains regarding the engraftment, proliferation, and differentiation for repopulating MSCs in recipient tissues. Therefore, we investigated the paracrine and/or endocrine role of MSCs in experimental colitis.We analyzed the therapeutic effects of MSC-conditioned medium (MSC-CM) on dextran sulfate sodium (DSS)- or 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. We investigated the effects of MSC-CM on the epithelial cell viability, mobility, cell cycle, and cytokine production in ex vivo lamina propria/mesenteric lymphocytes, a macrophage cell line, and the mixed lymphocyte reaction. An optimal regimen against colitis was explored. The contents of MSC-CM were analyzed using a WNT signaling pathway polymerase chain reaction array, an inflammatory cytokines antibody array, and liquid chromatography-tandem mass spectrometry analysis.Independent of the systemic administration route, MSC-CM concentrates were effective for the inductive phase of TNBS-induced colitis and for the recovery phase of DSS-induced colitis. Hypoxia appeared to be one of the optimal preconditioning factors assessed by cell motility and viability through activating the PI3K-Akt pathway in rat small intestine epithelial cells, IEC-6. Thus, Hypoxia had profound effects on the contents of MSC-CM, which comprised pleiotropic gut trophic factors involved in each wound healing process, including the anti-inflammatory, proliferative, and tissue remodeling phases.Identification and optimization of potential gut trophic factors in MSC-CM is urgently needed to form the basis for new drug discovery and for optimizing cell-based therapies for inflammatory bowel disease.