1 Regenerative Medicine Research Laboratories, FUJIFILM Corporation, Kanagawa, Japan.
Cell Transplant. 2018 Sep;27(9):1390-1400. doi: 10.1177/0963689718782442. Epub 2018 Jul 6.
Cell therapies using adipose-derived stem cells (ADSCs) have been used to treat inflammatory bowel disease (IBD) in human and dog. We previously reported the CellSaic technique, which uses a recombinant scaffold to enhance the efficacy of cell therapy. To examine whether this technique can be applied to cell therapy for colitis, we evaluated the efficacy of CellSaic in colitis mouse models. Colitis mouse models were developed by administering dextran sulfate sodium (DSS) to C57BL/6 mice for 7 days. Then CellSaic comprising human/canine ADSCs (1.2 × 10 cells) or human/canine ADSCs only (1.2 × 10 cells) were administered to the mice. The body weights were measured, and the colon length measurements and histological evaluations were conducted at 7 days after administration. After in vitro culture of human ADSC (hADSC) CellSaic and hADSC spheroids in medium containing TNFα, the levels of the anti-inflammatory protein TSG-6 in each supernatant were measured. Furthermore, we conducted tumorigenicity and general toxicity tests of canine ADSC (cADSC) CellSaic in NOG mice for 8 weeks. In the colitis mouse models, the ADSC CellSaic group presented recovery of body weight and colon length compared with the ADSC-only group. Histological analysis showed that ADSC CellSaic decreased the number of inflammatory cells and repaired ulceration. In vitro, hADSC CellSaic secreted 3.1-fold more TSG-6 than the hADSCs. In addition, tumorigenicity and general toxicity of cADSC CellSaic were not observed. This study suggests that human and canine ADSC CellSaic has a therapeutic effect of colitis in human and dogs.
脂肪来源干细胞 (ADSCs) 的细胞疗法已被用于治疗人类和犬的炎症性肠病 (IBD)。我们之前报道了 CellSaic 技术,该技术使用重组支架来增强细胞疗法的疗效。为了研究该技术是否可应用于结肠炎的细胞治疗,我们评估了 CellSaic 在结肠炎小鼠模型中的疗效。通过给 C57BL/6 小鼠施用葡聚糖硫酸钠 (DSS) 7 天来建立结肠炎小鼠模型。然后向小鼠施用包含人/犬 ADSCs(1.2×10 个细胞)或仅人/犬 ADSCs(1.2×10 个细胞)的 CellSaic。在给药后 7 天测量体重,并进行结肠长度测量和组织学评估。在 TNFα 存在的培养基中体外培养人 ADSC(hADSC)CellSaic 和 hADSC 球体后,测量每个上清液中的抗炎蛋白 TSG-6 的水平。此外,我们在 NOG 小鼠中进行了 8 周的犬 ADSC(cADSC)CellSaic 的致瘤性和一般毒性测试。在结肠炎小鼠模型中,与仅 ADSC 组相比,ADSC CellSaic 组体重和结肠长度恢复。组织学分析显示 ADSC CellSaic 减少了炎症细胞的数量并修复了溃疡。体外,hADSC CellSaic 分泌的 TSG-6 比 hADSCs 多 3.1 倍。此外,未观察到 cADSC CellSaic 的致瘤性和一般毒性。这项研究表明,人源和犬源 ADSC CellSaic 对人和犬的结肠炎具有治疗作用。