Abstract：
Inflammatory bowel disease (IBD) is a chronic gut inflammation with periods of acute flares and remission. Beneficial effects of a single dose of mesenchymal stem cell (MSC)-based treatment have been demonstrated in acute models of colitis. No studies investigated therapeutic effects of MSCs for the attenuation of enteric neuropathy in a chronic model of colitis. The short and long-term effects of MSC treatment in modulating inflammation and damage to the enteric nervous system (ENS) were studied in the Winnie mouse model of spontaneous chronic colitis highly representative of human IBD. Winnie mice received a single dose of either 1 × 106 human bone marrow-derived MSCs or 100µL PBS by intracolonic enema. C57BL/6 mice received 100µL PBS. Colon tissues were collected at 3 and 60 days post MSC administration to evaluate the short-term and long-term effects of MSCs on inflammation and enteric neuropathy by histological and immunohistochemical analyses. In a separate set of experiments, multiple treatments with 4 × 106 and 2 × 106 MSCs were performed and tissue collected at 3 days post treatment. Chronic intestinal inflammation in Winnie mice was associated with persistent diarrhea, perianal bleeding, morphological changes, and immune cell infiltration in the colon. Significant changes to the ENS, including impairment of cholinergic, noradrenergic and sensory innervation, and myenteric neuronal loss were prominent in Winnie mice. Treatment with a single dose of bone marrow-derived MSCs was ineffective in attenuating chronic inflammation and enteric neuropathy in Winnie.
摘要：
炎症性肠病（IBD）是一种慢性肠道炎症，伴有急性发作和缓解期。在结肠炎的急性模型中已经证明了单剂量的基于间充质干细胞(MSC)的治疗的有益效果。没有研究调查MSC在结肠炎慢性模型中减轻肠神经病的治疗效果。在高度代表人类IBD的自发性慢性结肠炎的Winnie小鼠模型中研究了MSC治疗在调节炎症和肠神经系统（ENS）损伤中的短期和长期作用。Winnie小鼠通过结肠内灌肠接受单剂量的1×106人骨髓来源的MSC或100μLPBS。C57BL/6小鼠接受100μLPBS。在MSC施用后3天和60天收集结肠组织以通过组织学和免疫组织化学分析评估MSC对炎症和肠神经病变的短期和长期作用。在一组单独的实验中，使用4×106和2×106个MSCs进行多次治疗,并在治疗后3天收集组织.Winnie小鼠的慢性肠道炎症与持续性腹泻有关，肛周出血,形态变化,和结肠中的免疫细胞浸润。ENS的重大变化，包括胆碱能损伤，去甲肾上腺素能和感觉神经支配，在Winnie小鼠中，肌间神经元丢失明显。在Winnie中，使用单剂量的骨髓来源的MSC治疗在减轻慢性炎症和肠神经病方面无效。
