An Increase in CD3+CD4+CD25+Regulatory T Cells after Administration of Umbilical Cord-Derived Mesenchymal Stem Cells during Sepsis

被引：65

作者：

Chao, Yu-Hua ^{[1
,2
,3
]}

Wu, Han-Ping ^{[4
,5
]}

Wu, Kang-Hsi ^{[6
,7
]}

Tsai, Yi-Giien ^{[3
,8
,9
]}

Peng, Ching-Tien ^{[6
,7
,10
]}

Lin, Kuan-Chia ^{[11
,12
]}

Chao, Wan-Ru ^{[1
,3
,13
]}

Lee, Maw-Sheng ^{[1
,14
]}

Fu, Yun-Ching ^{[15
,16
]}

机构：

[1] Chung Shan Med Univ, Inst Med, Taichung, Taiwan

[2] Chung Shan Med Univ Hosp, Dept Pediat, Taichung, Taiwan

[3] Chung Shan Med Univ, Sch Med, Taichung, Taiwan

[4] Buddhist Med Fdn, Taichung Tzuchi Hosp, Dept Pediat, Taichung, Taiwan

[5] Tzu Chi Univ, Dept Med, Hualien, Taiwan

[6] China Med Univ, Sch Chinese Med, Taichung, Taiwan

[7] China Med Univ, China Med Univ Hosp, Childrens Hosp, Dept Hematooncol, Taichung, Taiwan

[8] Changhua Christian Hosp, Dept Pediat, Changhua, Taiwan

[9] Kaohsiung Med Univ, Sch Med, Kaohsiung, Taiwan

[10] Asia Univ, Dept Biotechnol & Bioinformat, Taichung, Taiwan

[11] Natl Taipei Univ Nursing & Hlth Sci, Sch Nursing, Taipei, Taiwan

[12] Natl Taipei Univ Nursing & Hlth Sci, Life Course Epidemiol & Human Dev Res Grp, Taipei, Taiwan

[13] Chung Shan Med Univ Hosp, Dept Pathol, Taichung, Taiwan

[14] Chung Shan Med Univ Hosp, Dept Obstet & Gynecol, Taichung, Taiwan

[15] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[16] Taichung Vet Gen Hosp, Dept Pediat, Taichung, Taiwan

来源：

PLOS ONE | 2014年 / 9卷 / 10期

关键词：

STROMAL CELLS; BACTERIAL CLEARANCE; SURVIVAL; COTRANSPLANTATION; REDUCE; TRANSPLANTATION; INFLAMMATION; MECHANISMS; GENERATION; MSCS;

D O I：

10.1371/journal.pone.0110338

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs) have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP) model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by determining the changes of circulating inflammation-associated cytokine profiles and peripheral blood mononuclear cells 18 hours after CLP-induced sepsis. In vitro, bone marrow-derived MSCs (BMMSCs) and umbilical cord-derived MSCs (UCMSCs) showed a similar morphology and surface marker expression. UCMSCs had stronger potential for osteogenesis but lower for adipogenesis than BMMSCs. Compared with rats receiving PBS only after CLP, the percentage of circulating CD3+CD4+CD25+ regulatory T (Treg) cells and the ratio of Treg cells/T cells were elevated significantly in rats receiving MSCs. Further experiment regarding Treg cell function demonstrated that the immunosuppressive capacity of Treg cells from rats with CLP-induced sepsis was decreased, but could be restored by administration of MSCs. Compared with rats receiving PBS only after CLP, serum levels of interleukin-6 and tumor necrosis factor-a were significantly lower in rats receiving MSCs after CLP. There were no differences between BMMSCs and UCMSCs. In summary, this work provides the first in vivo evidence that administering BMMSCs or UCMSCs to rats with CLP-induced sepsis could increase circulating CD3+CD4+CD25+ Treg cells and Treg cells/T cells ratio, enhance Treg cell suppressive function, and decrease serum levels of interleukin-6 and tumor necrosis factor-a, suggesting the immunomodulatory association of Treg cells and MSCs during sepsis.

引用

页数：8

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