首页> 外文期刊>Stem cells translational medicine. >Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose‐Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model
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Mesenchymal Stem Cells (MSC) Derived from Induced Pluripotent Stem Cells (iPSC) Equivalent to Adipose‐Derived MSC in Promoting Intestinal Healing and Microbiome Normalization in Mouse Inflammatory Bowel Disease Model

机译:诱导多能干细胞(iPSC)与脂肪来源的MSC等效的间充质干细胞(MSC)在小鼠炎症性肠病模型中促进肠道愈合和微生物组正常化

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Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has emerged as a promising new therapeutic strategy for managing inflammatory bowel disease (IBD). However, MSC therapy ideally requires a convenient and relatively homogenous cell source (typically bone marrow or adipose tissues) and the ability to generate cells with stable phenotype and function. An alternative means of generating allogeneic MSC is to derive them from induced pluripotent stem cells (iPSC), which could in theory provide an indefinite supply of MSC with well‐defined phenotype and function. Therefore, we compared the effectiveness of iPSC‐derived MSC (iMSC) and adipose‐derived MSC (adMSC) in a mouse model of IBD (dextran sodium sulfate‐induced colitis), and investigated mechanisms of intestinal protection. We found that iMSC were equivalent to adMSC in terms of significantly improving clinical abnormalities in treated mice and reducing lesion scores and inflammation in the gut. Administration of iMSC also stimulated significant intestinal epithelial cell proliferation, increased in the numbers of Lgr5+ intestinal stem cells, and increased intestinal angiogenesis. In addition, the microbiome alterations present in mice with colitis were partially restored to resemble those of healthy mice following treatment with iMSC or adMSC. Thus, iMSC administration improved overall intestinal health and healing with equivalent potency to treatment with adMSC. This therefore is the first report of the effectiveness of iMSC in the treatment of IBD, along with a description of unique mechanisms of action with respect to intestinal healing and microbiome restoration. Stem Cells Translational Medicine 2018;7:456–467
机译:异体或自体间充质干细胞(MSC)的细胞疗法已成为一种有希望的新的治疗炎症性肠病(IBD)的治疗策略。然而,理想地,MSC疗法需要方便且相对同质的细胞来源(通常是骨髓或脂肪组织),以及产生具有稳定表型和功能的细胞的能力。生成同种异体MSC的另一种方法是从诱导多能干细胞(iPSC)衍生它们,从理论上讲,它可以无限期供应具有明确表型和功能的MSC。因此,我们在IBD(右旋糖酐硫酸钠诱发的结肠炎)小鼠模型中比较了iPSC来源的MSC(iMSC)和脂肪来源的MSC(adMSC)的有效性,并研究了肠道保护机制。我们发现,iMSC与adMSC相当,可显着改善治疗小鼠的临床异常状况并减少病变评分和肠道炎症。 iMSC的使用还刺激了肠道上皮细胞的显着增殖,增加了Lgr5 +肠道干细胞的数量,并增加了肠道血管生成。另外,结肠炎小鼠中存在的微生物组改变被部分恢复,类似于健康小鼠经iMSC或adMSC治疗后的改变。因此,iMSC给药可改善整体肠道健康和愈合,其功效与adMSC疗法相当。因此,这是关于iMSC治疗IBD有效性的第一份报告,并描述了肠道修复和微生物组修复的独特作用机制。干细胞转化医学2018; 7:456–467

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