DataSheet2_Rejuvenation of Helicobacter pylori–Associated Atrophic Gastritis Through Concerted Actions of Placenta-Derived Mesenchymal Stem Cells Prevented Gastric Cancer.PDF

Chronic Helicobacter pylori infection causes gastric cancer via the progression of precancerous chronic atrophic gastritis (CAG). Therefore, repairing gastric atrophy could be a useful strategy in preventing H. pylori–associated gastric carcinogenesis. Although eradication of the bacterial pathogen offers one solution to this association, this study was designed to evaluate an alternative approach using mesenchymal stem cells to treat CAG and prevent carcinogenesis. Here, we used human placenta-derived mesenchymal stem cells (PD-MSCs) and their conditioned medium (CM) to treat H. pylori–associated CAG in a mice/cell model to explore their therapeutic effects and elucidate their molecular mechanisms. We compared the changes in the fecal microbiomes in response to PD-MSC treatments, and chronic H. pylori–infected mice were given ten treatments with PD-MSCs before being sacrificed for end point assays at around 36 weeks of age. These animals presented with significant reductions in the mean body weights of the control group, which were eradicated following PD-MSC treatment (p < 0.01). Significant changes in various pathological parameters including inflammation, gastric atrophy, erosions/ulcers, and dysplastic changes were noted in the control group (p < 0.01), but these were all significantly reduced in the PD-MSC/CM-treated groups. Lgr5+, Ki-67, H+/K+-ATPase, and Musashi-1 expressions were all significantly increased in the treated animals, while inflammatory mediators, MMP, and apoptotic executors were significantly decreased in the PD-MSC group compared to the control group (p < 0.001). Our model showed that H. pylori–initiated, high-salt diet–promoted gastric atrophic gastritis resulted in significant changes in the fecal microbiome at the phylum/genus level and that PD-MSC/CM interventions facilitated a return to more normal microbial communities. In conclusion, administration of PD-MSCs or their conditioned medium may present a novel rejuvenating agent in preventing the progression of H. pylori–associated premalignant lesions.

慢性幽门螺杆菌（Helicobacter pylori, H. pylori）感染可通过癌前慢性萎缩性胃炎（chronic atrophic gastritis, CAG）的进展诱发胃癌。因此，修复胃萎缩或可成为预防幽门螺杆菌相关性胃癌发生的有效策略。尽管根除该致病菌可为该关联问题提供一种解决方案，但本研究旨在评估一种替代方案：利用间充质干细胞治疗CAG并预防癌变发生。本研究采用人胎盘来源间充质干细胞（placenta-derived mesenchymal stem cells, PD-MSCs）及其条件培养基（conditioned medium, CM），在小鼠/细胞模型中干预幽门螺杆菌相关CAG，以探究其治疗效应并阐明其分子机制。我们对比了PD-MSCs治疗后粪便微生物组的变化；慢性幽门螺杆菌感染小鼠经10次PD-MSCs治疗后，于约36周龄时处死以开展终点检测。对照组小鼠的平均体重出现显著降低，而PD-MSCs治疗可消除该体重下降现象（p < 0.01）。对照组小鼠在炎症、胃萎缩、糜烂/溃疡及异型增生等多项病理参数上均出现显著改变（p < 0.01），但PD-MSCs/条件培养基治疗组的上述病理改变均得到显著改善。与对照组相比，治疗组小鼠的Lgr5+、Ki-67、H+/K+-ATP酶及Musashi-1的表达水平均显著升高，而炎症介质、基质金属蛋白酶（matrix metalloproteinase, MMP）及凋亡执行因子的表达则显著下调（p < 0.001）。本研究模型证实，幽门螺杆菌启动、高盐饮食促进的萎缩性胃炎可在门/属分类水平上引发粪便微生物组的显著改变，而PD-MSCs/条件培养基干预可促使微生物群落恢复至更接近正常的状态。综上，输注人胎盘来源间充质干细胞或其条件培养基或可成为一种新型修复制剂，用于预防幽门螺杆菌相关癌前病变的进展。