CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair

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• 作者：Changjiang Hu ; PhD^a ; ^b ; ¹ ; Xin Yong ; PhD^a ; ^b ; ¹ ; Changzhu Li ; PhD^a ; ^{changzhu.li@163.com} ; Muhan Lü ; PhD^b ; Dengqun Liu ; PhD^c ; Lin Chen ; PhD^b ; Jiongyu Hu ; PhD^a ; Miao Teng ; PhD^a ; Dongxia Zhang ; PhD^a ; Yahan Fan ; PhD^b ; Guangping Liang ; PhD^a ; ^{gpl12@yahoo.cn}
• 关键词：Bone marrow&ndash ; derived mesenchymal stem cells ; Burn wound ; CXCL12 ; CXCR4
• 刊名：Journal of Surgical Research
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：183
• 期：1
• 页码：427-434
• 全文大小：2189 K

文摘

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.