Therapeutic potential of mature adipocyte-derived dedifferentiated fat cells for inflammatory bowel disease
Therapeutic potential of mature adipocyte-derived dedifferentiated fat cells for inflammatory bowel disease
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DOI：
10.1007/s00383-020-04681-5
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发表时间：
2020-05-24
影响因子：
1.8
通讯作者：
Matsumoto, Taro
中科院分区：
文献类型：
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作者：
Ishioka, Shigeki;Hosokawa, Takashi;Matsumoto, Taro
目的本实验室前期研究表明，成熟脂肪细胞来源的去分化脂肪细胞（DFAT）具有与间充质干细胞相似的多能性。在这里，我们研究了DFAT细胞在体外的免疫调节潜力和DFAT细胞移植在小鼠炎症性肠病（IBD）模型中的治疗效果。方法观察DFAT细胞共培养对T细胞增殖及免疫抑制相关基因表达的影响。为了产生IBD，将CD4（+）CD45RB（高）T细胞腹膜内注射到SCID小鼠中。一周后，腹膜内注射DFAT细胞（1 × 10（5），DFAT组）或盐水（对照组）。随后每周测量体重，并在T细胞施用后5周评价IBD临床和组织学评分。结果共培养的DFAT细胞对T细胞增殖有抑制作用，且呈细胞密度依赖性。TNF α刺激可上调DFAT细胞中TRAIL、IDO 1和NOS 2的基因表达。与对照组相比，DFAT组改善了IBD相关的体重减轻、IBD临床和组织学评分。结论DFAT细胞具有免疫调节作用，细胞移植可促进IBD模型结肠损伤的修复，改善临床症状。DFAT细胞可能在IBD的治疗中发挥重要作用。
Purpose Our previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model. Methods The effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4(+)CD45RB(high) T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 x 10(5), DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration. Results The T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNF alpha stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group. Conclusion DFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.