Chen Qi, Liu Fengqi, Zhang Gaochao, Qu Qingyuan, Chen Yuxiu, Li Menglin, Huang Qiusha, Fu Haixia, Zhu Xiaolu, He Yun, Huang Xiaojun, Zhang Xiaohui
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Clinical Research Center for Hematologic Disease, Beijing, China.
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Clinical Research Center for Hematologic Disease, Beijing, China.
J Thromb Haemost. 2025 Apr;23(4):1428-1441. doi: 10.1016/j.jtha.2024.12.027. Epub 2025 Jan 3.
Immune thrombocytopenia during pregnancy (PITP) is the most common cause of platelet reduction in early and mid-pregnancy. However, the pathogenesis of PITP is still unclear.
To determine the characteristics of bone marrow mesenchymal stem cells (BM-MSCs) in PITP patients and to explore the associations between metabolites, the gut microbiota, and BM-MSCs in PITP.
The characteristics of BM-MSCs were detected through in vitro and in vivo experiments. Nontargeted metabolomics was used to screen metabolites. The features of the gut microbiota were analyzed by 16S rDNA sequencing. PITP and fecal microbiota transplantation (FMT) mouse model were established to explore the associations between metabolites, gut microbiota, and BM-MSCs.
BM-MSCs from PITP patients had significant senescence and apoptosis, as well as impaired immunoregulatory function. Metabolomic analysis indicated that progesterone was the most significant specific metabolite in PITP patients. In vivo studies showed that progesterone mediated MSC injury. Further analysis of the gut microbiota and FMT experiments revealed that progesterone mediated BM-MSCs injury by regulating the composition of the gut microbiota in PITP. RNA sequencing analysis of BM-MSCs from FMT mice revealed abnormal expression of genes related to cell aging and the NOD-like receptor signaling pathway.
In conclusion, BM-MSCs in the PITP were significantly impaired, which was associated with increased progesterone and changes in the gut microbiota regulated by progesterone. Intervening with the gut microbiota may become a new treatment for PITP.
妊娠期免疫性血小板减少症（PITP）是妊娠早期和中期血小板减少的最常见原因。然而，PITP的发病机制仍不清楚。
确定PITP患者骨髓间充质干细胞（BM-MSCs）的特征，并探讨PITP中代谢物、肠道微生物群与BM-MSCs之间的关联。
通过体外和体内实验检测BM-MSCs的特征。采用非靶向代谢组学筛选代谢物。通过16S rDNA测序分析肠道微生物群的特征。建立PITP和粪便微生物群移植（FMT）小鼠模型，以探讨代谢物、肠道微生物群与BM-MSCs之间的关联。
PITP患者的BM-MSCs有明显的衰老和凋亡，以及免疫调节功能受损。代谢组学分析表明，孕酮是PITP患者中最显著的特异性代谢物。体内研究表明，孕酮介导间充质干细胞损伤。对肠道微生物群和FMT实验的进一步分析表明，孕酮通过调节PITP患者的肠道微生物群组成来介导BM-MSCs损伤。对FMT小鼠的BM-MSCs进行RNA测序分析，发现与细胞衰老和NOD样受体信号通路相关的基因表达异常。
总之，PITP中的BM-MSCs明显受损，这与孕酮增加以及孕酮调节的肠道微生物群变化有关。干预肠道微生物群可能成为PITP的一种新的治疗方法。
