Miyamoto Shuichi, Ohnishi Shunsuke, Onishi Reizo, Tsuchiya Ikuki, Hosono Hidetaka, Katsurada Takehiko, Yamahara Kenichi, Takeda Hiroshi, Sakamoto Naoya
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University Sapporo, Japan.
Laboratory of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan.
Am J Transl Res. 2017 Mar 15;9(3):940-952. eCollection 2017.
Cell therapy with mesenchymal stem cells (MSCs) is expected to provide a new strategy for the treatment of inflammatory bowel disease (IBD). Large amounts of MSCs can be obtained from human amnion. Therefore, we investigated the effect of transplantation of human amnion-derived MSCs (hAMSCs) or enema of conditioned medium (CM) from hAMSCs into rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. In the first experiment, 10-week-old male Sprague-Dawley rats were intravenously injected with hAMSCs (1 × 10 cells) 3 h after rectal administration of TNBS (45 mg/kg). In the second experiment, rats with TNBS-induced colitis received CM by enema into the colon for 3 days. Colitis was investigated by endoscopy, histology, immunohistochemistry, and by measuring mRNA expression of inflammatory mediators. Administration of hAMSCs or CM enema significantly improved the endoscopic score. In addition, these two interventions resulted in significantly decreased infiltration of neutrophils and monocytes/macrophages and decreased expression levels of TNF-α, CXCL1, and CCL2. In conclusion, transplantation of hAMSCs and CM enema provided significant improvement in rats with TNBS-induced colitis. CM from hAMSCs and hAMSCs may be new strategies for the treatment of IBD.
间充质干细胞（MSCs）的细胞疗法有望为炎症性肠病（IBD）的治疗提供一种新策略。人羊膜可获取大量的间充质干细胞。因此，我们研究了将人羊膜来源的间充质干细胞（hAMSCs）移植或其条件培养基（CM）灌肠给予2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎大鼠后的效果。在第一个实验中，10周龄雄性Sprague-Dawley大鼠在直肠给予TNBS（45 mg/kg）3小时后静脉注射hAMSCs（1×10个细胞）。在第二个实验中，TNBS诱导的结肠炎大鼠接受CM灌肠至结肠，持续3天。通过内镜检查、组织学、免疫组织化学以及测量炎症介质的mRNA表达来研究结肠炎情况。给予hAMSCs或CM灌肠显著改善了内镜评分。此外，这两种干预措施导致中性粒细胞和单核细胞/巨噬细胞浸润显著减少，以及TNF-α、CXCL1和CCL2的表达水平降低。总之，hAMSCs移植和CM灌肠使TNBS诱导的结肠炎大鼠有显著改善。hAMSCs的CM和hAMSCs可能是治疗IBD的新策略。
