Fu Zheng-Wei, Zhang Zhen-Yu, Ge Hai-Yan
Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of MedicineShanghai, China.
Am J Transl Res. 2018 Jan 15;10(1):54-66. eCollection 2018.
Efficient delivery routes are critical for the effectiveness of adipose-derived mesenchymal stem cells (ADMSCs) in treating inflammatory bowel disease (IBD). Conventional ADMSC delivery routes include local, intravenous and intraperitoneal injection. Whether mesenteric injection has potential in IBD treatment remains unknown. In the present study, we investigated the therapeutic effects of mesenteric injection of ADMSCs in a trinitrobenzene sulfonic acid-induced rat IBD model and explored whether this treatment affected T helper 17 (Th17)/regulatory T (Treg) cell ratio. The results showed that mesenteric injection of ADMSCs markedly reduced signs of colitis, colon shortening, weight loss and pathological damage. The treatment also decreased serum tumor necrosis factor alpha concentration, increased serum tumor necrosis factor alpha-stimulated gene protein 6 concentration, and augmented repair via proliferation (assessed by evaluating Ki-67 levels) in colonic tissue. Moreover, mesenteric injection of ADMSCs reduced interleukin (IL)-17A and IL-6 mRNA expression, and increased IL-10 and transforming growth factor-beta mRNA expression in colonic tissue. Protein analyses indicated that mesenteric injection of ADMSCs was associated with increased expression of forkhead box P3 and IL-10 as well as decreased expression of retinoid-related orphan receptor λt and IL-17. Additionally, the treatment inhibited phosphorylation of signal transducer and activator of transcription (STAT) 3 and activated phosphorylation of STAT5. Taken together, these results suggest that mesenteric injection of ADMSCs is a promising approach to treating trinitrobenzene sulfonic acid-induced IBD, and achieves its therapeutic effect by regulating the pro/anti-inflammatory Th17/Treg cell balance.
有效的递送途径对于脂肪来源的间充质干细胞（ADMSC）治疗炎症性肠病（IBD）的有效性至关重要。传统的ADMSC递送途径包括局部、静脉内和腹腔内注射。肠系膜注射在IBD治疗中是否具有潜力仍不清楚。在本研究中，我们在三硝基苯磺酸诱导的大鼠IBD模型中研究了肠系膜注射ADMSC的治疗效果，并探讨了这种治疗是否影响辅助性T细胞17（Th17）/调节性T（Treg）细胞比例。结果表明，肠系膜注射ADMSC显著减轻了结肠炎的症状、结肠缩短、体重减轻和病理损伤。该治疗还降低了血清肿瘤坏死因子α浓度，增加了血清肿瘤坏死因子α刺激基因蛋白6浓度，并通过结肠组织中的增殖（通过评估Ki-67水平）增强了修复。此外，肠系膜注射ADMSC降低了结肠组织中白细胞介素（IL）-17A和IL-6 mRNA表达，并增加了IL-10和转化生长因子-β mRNA表达。蛋白质分析表明，肠系膜注射ADMSC与叉头框P3和IL-10表达增加以及视黄酸相关孤儿受体λt和IL-17表达降低有关。此外，该治疗抑制了信号转导和转录激活因子（STAT）3的磷酸化并激活了STAT5的磷酸化。综上所述，这些结果表明，肠系膜注射ADMSC是治疗三硝基苯磺酸诱导的IBD的一种有前景的方法，并通过调节促炎/抗炎Th17/Treg细胞平衡实现其治疗效果。
