CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair
CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair
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DOI：
10.1016/j.jss.2013.01.019
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发表时间：
2013-07-01
影响因子：
2.2
通讯作者：
Liang, Guangping
中科院分区：
文献类型：
--
作者：
Hu, Changjiang;Yong, Xin;Liang, Guangping
背景：骨髓间充质干细胞（BM-MSCs）在组织修复中起着重要作用。方法：将转绿色荧光蛋白基因雄性小鼠的BM-MSCs输注给受照雌性C57 BL/6小鼠。21天后，雌性小鼠被烧伤。通过体内荧光成像系统测量烧伤面积的大小，并通过荧光原位杂交和免疫荧光技术估计BM-MSC的趋化性和上皮形成。采用酶联免疫吸附法和免疫组化法检测CXCL 12和CXCR 4在创面组织中的表达。通过阻断CXCR 4，进一步评价CXCL 12/CXCR 4信号在BM-MSC趋化中的重要性。荧光原位杂交和免疫荧光技术检测到来自绿色荧光蛋白转基因小鼠的Y染色体阳性细胞与角蛋白共定位。酶联免疫吸附试验显示烧伤后BM-MSC治疗的嵌合小鼠伤口部位CXCL 12和CXCR 4蛋白水平升高。免疫组化还显示，CXCL 12水平升高，在烧伤后第7天与0天相比。结论：BM-MSC向烧伤创面的迁移促进了创面的上皮化，BM-MSC的迁移是由CXCL 12/CXCR 4信号通路介导的。(C)2013 Elsevier Inc. All rights reserved.
Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play a crucial role in tissue repair. Their role in thermal burn wound regeneration and the relevant mechanism, however, is rarely studied.Methods: BM-MSCs from green fluorescent protein transgenic male mice were transfused to irradiated recipient female C57BL/6 mice. Twenty-one days later, the female mice were inflicted with burn wounds. The size of the burned area was measured by an in vivo fluorescence imaging system, and BM-MSC chemotaxis and epithelialization were estimated by fluorescence in situ hybridization and immunofluorescence technology. The expression of CXCL12 and CXCR4 in the wound margin was detected by enzyme-linked immunosorbent assay and immunohistochemistry. The importance of CXCL12/CXCR4 signaling in BM-MSC chemotaxis was further estimated by blocking CXCR4 in vivo and in vitro.Results: In vivo imaging results showed that BM-MSCs migrated to the injured margins. Fluorescence in situ hybridization and immunofluorescence technology revealed that Y chromosome-positive cells derived from green fluorescent protein transgenic mice were detected to be colocalized with keratin protein. Enzyme-linked immunosorbent assay revealed increased levels of CXCL12 and CXCR4 protein in the wound sites of BM-MSC-treated chimeric mice after burn. Immunohistochemistry also disclosed that CXCL12 levels were elevated at postburn day 7 compared with day 0. Furthermore, pretreatment of the BM-MSCs with the CXCR4 antagonist AMD3100 significantly inhibited the mobilization of BM-MSCs in vitro and in vivo, which attenuated wound closure.Conclusion: BM-MSC migration to the burned margins promotes the epithelialization of the wound, and mobilization of BM-MSCs is mediated by CXCL12/CXCR4 signaling. (C) 2013 Elsevier Inc. All rights reserved.