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Therapeutic Effects of Mesenchymal Stem Cells Derived From Bone Marrow, Umbilical Cord Blood, and Pluripotent Stem Cells in a Mouse Model of Chemically Induced Inflammatory Bowel Disease

机译:在化学诱导的炎症肠疾病小鼠模型中源自骨髓,脐带血和多能干细胞中间充质干细胞的治疗作用

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Acute inflammatory bowel disease (AIBD) is a wide clinical entity including severe gastrointestinal pathologies with common histopathological basis. Epidemiologically increasing diseases, such as necrotizing enterocolitis (NEC), gastrointestinal graft versus host disease (GVHD), and the primary acute phase of chronic inflammatory bowel disease (CIBD), exhibit a high necessity for new therapeutic strategies. Mesenchymal stem cell (MSC) cellular therapy represents a promising option for the treatment of these diseases. In our study, we comparatively assess the efficacy of human MSCs derived from bone marrow (BM), umbilical cord blood (UCB), human embryonic stem cells (ESCs), or human-induced pluripotent stem cells (iPSCs) in a mouse model of chemically induced acute enterocolitis. The laboratory animals were provided ad libitum potable dextrane sulfate sodium solution (DSS) in order to reproduce an AIBD model and then individually exposed intraperitoneally to MSCs derived from BM (BM-MSCs), UCB (UCB-MSCs), ESCs (ESC-MSCs), or iPSCs (iPSC-MSCs). The parameters used to evaluate the cellular treatment efficacy were the animal survival prolongation and the histopathological-macroscopic picture of bowel sections. Although all categories of mesenchymal stem cells led to statistically significant survival prolongation compared to the control group, significant clinical and histopathological improvement was observed only in mice receiving BM-MSCs and UCB-MSCs. Our results demonstrated that the in vivo anti-inflammatory effect of ESC-MSCs and iPSC-MSCs was inferior to that of UCB-MSCs and BM-MSCs. Further investigation will clarify the potential of ESCs and iPSC-derived MSCs in AIBD treatment.
机译:急性炎症性肠病(AIBD)是一种庞大的临床实体,包括具有常见组织病理学基础的严重胃肠病理学。流行病学性增加的疾病,如坏死性小肠结肠炎(NEC),胃肠移植物与宿主疾病(GVHD)和慢性炎症肠道疾病(CIBD)的原发性急性期,表现出新的治疗策略的高必然。间充质干细胞(MSC)细胞疗法代表了治疗这些疾病的有希望的选择。在我们的研究中,我们在小鼠模型中相比评估了来自骨髓(BM),脐带血(UCB),人胚胎干细胞(ESC)或人诱导的多能干细胞(IPSC)的人胚胎血液(UCB),人胚胎干细胞(ESC)或人诱导的多能干细胞(IPSC)的疗效化学诱导的急性内肠结肠炎。为实验室动物提供AD Libitum Potable Dextrane硫酸钠钠溶液(DSS),以便再现AIBD模型,然后单独暴露于腹腔内衍生自BM(BM-MSCs),UCB(UCB-MSCs),ESC的MSCs(ESC-MSCs )或IPSCS(IPSC-MSCS)。用于评估细胞治疗疗效的参数是动物存活延长和肠切片的组织病理学 - 宏观图。尽管与对照组相比,所有类别的间充质干细胞导致统计上显着的存活延长,但仅在接受BM-MSC和UCB-MSCs的小鼠中观察到显着的临床和组织病理学改善。我们的研究结果表明,ESC-MSC和IPSC-MSCs的体内抗炎作用差别不如UCB-MSCs和BM-MSCs的缺陷效应。进一步调查将阐明AIBD治疗中ESC和IPSC衍生的MSCs的潜力。

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