Stromal Cell-Derived Factor-1 Receptor CXCR4-Overexpressing Bone Marrow Mesenchymal Stem Cells Accelerate Wound Healing by Migrating into Skin Injury Areas
Stromal Cell-Derived Factor-1 Receptor CXCR4-Overexpressing Bone Marrow Mesenchymal Stem Cells Accelerate Wound Healing by Migrating into Skin Injury Areas
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DOI：
10.1089/cell.2012.0046
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发表时间：
2013-06-01
影响因子：
1.6
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
--
作者：
Yang, Dazhi;Sun, Shijin;Zhang, Bo
基质细胞衍生因子-1（SDF-1）及其膜受体C-X-C趋化因子受体4（CXCR 4）参与多种干细胞类型的归巢和迁移、新生血管形成和细胞增殖。本研究探讨了骨髓间充质干细胞（BMSCs）通过在BMSCs中过表达CXCR 4来加速小鼠模型皮肤伤口愈合的假设。我们比较了BALB/c小鼠、严重联合免疫缺陷（SCID）小鼠和免疫系统缺陷裸小鼠在Co-60辐射诱导骨髓损伤后的SDF-1表达和皮肤伤口愈合时间。通过Y染色体标记物分析，将移植的腺病毒转染的CXCR 4过表达的雄性BMSCs在伤口区域中的发生与未转染的雄性BALB/c BMSCs在Co-60照射的雌性小鼠皮肤伤口愈合区域中的发生进行比较。BALB/c小鼠的伤口愈合时间为14.00 +/- 1.41天，而裸鼠和SCID小鼠的伤口愈合时间分别为17.16 +/- 1.17天和19.83 +/- 0.76天。CXCR 4过表达的BMSCs能促进小鼠创伤愈合。CXCR 4过表达的BMSC以SDF-1表达依赖的方式以增强的方式迁移到皮肤伤口，从而缩短皮肤伤口愈合时间。
Stromal cell-derived factor-1 (SDF-1) and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4) are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. This study investigated the hypothesis that bone marrow-derived mesenchymal stem cells (BMSCs) accelerate skin wound healing in the mouse model by overexpression of CXCR4 in BMSCs. We compared SDF-1 expression and skin wound healing times of BALB/c mice, severe combined immunodeficiency (SCID) mice, and immune system-deficient nude mice after Co-60 radiation-induced injury of their bone marrow. The occurrence of transplanted adenovirus-transfected CXCR4-overexpressing male BMSCs in the wound area was compared with the occurrence of untransfected male BALB/c BMSCs in Co-60-irradiated female mice skin wound healing areas by Y chromosome marker analyses. The wound healing time of BALB/c mice was 14.00 +/- 1.41 days, whereas for the nude and SCID mice it was 17.16 +/- 1.17 days and 19.83 +/- 0.76 days, respectively. Male BMSCs could be detected in the surrounding areas of Co-60-irradiated female BALB/c mice wounds, and CXCR4-overexpressing BMSCs accelerated the wound healing time. CXCR4-overexpressing BMSCs migrate in an enhanced manner to skin wounds in a SDF-1-expression-dependent manner, thereby reducing the skin wound healing time.