Mesenchymal stem cells stimulate intestinal stem cells to repair radiation-induced intestinal injury

被引:89
|
作者
Gong, Wei [1 ,2 ]
Guo, Mengzheng [1 ,2 ]
Han, Zhibo [2 ,3 ,4 ]
Wang, Yan [1 ,2 ]
Yang, Ping [5 ]
Xu, Chang [1 ,2 ]
Wang, Qin [1 ,2 ]
Du, Liqing [1 ,2 ]
Li, Qian [1 ,2 ]
Zhao, Hui [6 ,7 ,8 ]
Fan, Feiyue [1 ,2 ,9 ,10 ]
Liu, Qiang [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Tianjin Key Lab Radiat Med & Mol Nucl Med, Dept Radiobiol, Inst Radiat Med, 238 Baidi Rd, Tianjin 300192, Peoples R China
[2] Peking Union Med Coll, 238 Baidi Rd, Tianjin 300192, Peoples R China
[3] Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China
[4] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China
[5] Tianjin Inst Med & Pharmaceut Sci, Tianjin, Peoples R China
[6] Tianjin Univ Commerce, Tianjin Key Lab Food & Biotechnol, Sch Biotechnol & Food Sci, Tianjin, Peoples R China
[7] North China Univ Sci & Technol, Dept Hematol, Affiliated Hosp, Tangshan, Peoples R China
[8] North China Univ Sci & Technol, Translat Med Ctr, Affiliated Hosp, Tangshan, Peoples R China
[9] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China
[10] Peking Union Med Coll, Beijing, Peoples R China
来源
CELL DEATH & DISEASE | 2016年 / 7卷
基金
中国国家自然科学基金;
关键词
IN-VITRO; CRYPT; LGR5; POPULATIONS; MICE; ACTIVATION; EXPRESSION; EXPANSION; MARKERS; BMI1;
D O I
10.1038/cddis.2016.276
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The loss of stem cells residing in the base of the intestinal crypt has a key role in radiation-induced intestinal injury. In particular, Lgr(5+) intestinal stem cells (ISCs) are indispensable for intestinal regeneration following exposure to radiation. Mesenchymal stem cells (MSCs) have previously been shown to improve intestinal epithelial repair in a mouse model of radiation injury, and, therefore, it was hypothesized that this protective effect is related to Lgr(5+) ISCs. In this study, it was found that, following exposure to radiation, transplantation of MSCs improved the survival of the mice, ameliorated intestinal injury and increased the number of regenerating crypts. Furthermore, there was a significant increase in Lgr(5+) ISCs and their daughter cells, including Ki67(+) transient amplifying cells, Vil1(+) enterocytes and lysozyme(+) Paneth cells, in response to treatment with MSCs. Crypts isolated from mice treated with MSCs formed a higher number of and larger enteroids than those from the PBS group. MSC transplantation also reduced the number of apoptotic cells within the small intestine at 6 h post-radiation. Interestingly, Wnt3a and active beta-catenin protein levels were increased in the small intestines of MSC-treated mice. In addition, intravenous delivery of recombinant mouse Wnt3a after radiation reduced damage in the small intestine and was radioprotective, although not to the same degree as MSC treatment. Our results show that MSCs support the growth of endogenous Lgr5+ ISCs, thus promoting repair of the small intestine following exposure to radiation. The molecular mechanism of action mediating this was found to be related to increased activation of the Wnt/beta-catenin signaling pathway.
引用
收藏
页码:e2387 / e2387
页数:8
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