Center for Immune and Regenerative Medicine, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Stem Cells Transl Med. 2018 Jun;7(6):456-467. doi: 10.1002/sctm.17-0305. Epub 2018 Apr 10.
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.
异体或自体间充质干细胞（MSC）的细胞治疗已成为治疗炎症性肠病（IBD）的一种有前途的新治疗策略。然而，MSC 治疗理想上需要方便且相对同质的细胞来源（通常为骨髓或脂肪组织），并具有生成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）中获得它们，从理论上讲，这可以提供具有明确定义表型和功能的 MSC 的无限供应。因此，我们在 IBD 的小鼠模型（葡聚糖硫酸钠诱导的结肠炎）中比较了 iPSC 衍生的 MSC（iMSC）和脂肪衍生的 MSC（adMSC）的有效性，并研究了肠道保护的机制。我们发现，iMSC 在治疗小鼠中显著改善临床异常、降低肠道损伤评分和炎症方面与 adMSC 等效。iMSC 的给药还刺激了显著的肠上皮细胞增殖，增加了 Lgr5+肠干细胞的数量，并增加了肠血管生成。此外，在接受 iMSC 或 adMSC 治疗后，结肠炎小鼠中存在的微生物组改变部分恢复为类似于健康小鼠的状态。因此，iMSC 给药改善了整体肠道健康和愈合，其效力与 adMSC 治疗相当。因此，这是首次报道 iMSC 在治疗 IBD 中的有效性，并描述了与肠道愈合和微生物组恢复相关的独特作用机制。《干细胞转化医学》2018 年;7:456-467。
