Institute for Health and Sport, Victoria University; Western Centre for Health, Research and Education, Sunshine Hospital, Melbourne, VIC, Australia.
Department of Pediatric Surgery, Pediatric Surgery Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Cell Tissue Res. 2022 Jul;389(1):41-70. doi: 10.1007/s00441-022-03633-w. Epub 2022 May 10.
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 × 10 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 × 10 and 2 × 10 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.
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。单次间充质干细胞（MSC）治疗已在急性结肠炎模型中显示出有益效果。尚无研究调查 MSC 治疗对慢性结肠炎模型中肠神经病变的缓解作用。本研究在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）损伤方面的短期和长期作用，该模型高度代表了人类 IBD。Winnie 小鼠通过结肠内灌肠接受单次 1×10 个人骨髓来源的 MSC 或 100μL PBS。C57BL/6 小鼠接受 100μL PBS。在 MSC 给药后 3 和 60 天收集结肠组织，通过组织学和免疫组织化学分析评估 MSC 对炎症和肠神经病的短期和长期作用。在一组单独的实验中，进行了多次用 4×10 和 2×10 MSC 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、肛周出血、结肠形态改变和免疫细胞浸润有关。ENS 的显著变化，包括胆碱能、去甲肾上腺素能和感觉神经支配的损伤以及肌间神经元丢失，在 Winnie 小鼠中尤为明显。单次骨髓来源的 MSC 治疗不能减轻 Winnie 慢性炎症和肠神经病。
