Transplantation of menstrual blood-derived endometrial stem cells allevi-ates chemotherapy-induced intestinal injury and flora imbalance in mice through immunomodulation
10.3969/j.issn.1000-4718.2024.02.013
- VernacularTitle:经血源子宫内膜干细胞移植通过免疫调节缓解化疗引起的小鼠肠道损伤和菌群失调
- Author:
Qin LIU
1
,
2
;
Mengyuan CHANG
;
Haofeng SONG
;
Chenxu DU
;
Yonghai LI
;
Shenghui ZHANG
;
Yanli LIU
;
Juntang LIN
Author Information
1. 新乡医学院生命科学技术学院,河南 新乡 453003
2. 新乡医学院干细胞与生物治疗技术研究中心,河南 新乡 453003
- Keywords:
chemotherapy;
cisplatin;
menstrual blood-derived endometrial stem cells;
immunomodulation;
Intestinal flora
- From:
Chinese Journal of Pathophysiology
2024;40(2):301-308
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.
