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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >Enhanced recruitment and hematopoietic reconstitution of bone marrow-derived mesenchymal stem cells in bone marrow failure by the SDF-1/CXCR4
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Enhanced recruitment and hematopoietic reconstitution of bone marrow-derived mesenchymal stem cells in bone marrow failure by the SDF-1/CXCR4

机译：通过SDF-1 / CXCR4，增强骨髓源性间充质干细胞骨髓衍生间充质干细胞的招募和造血重建

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摘要

Aplastic anemia (AA) is a bone marrow failure disease. It is difficult to treat AA, and in addition, relapses are common because of its complex disease pathogenesis. Allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) infusion is an effective and safe treatment option for the AA patients. However, it found that BMSCs infusion in AA patients is less than 30% effective. Therefore, the key to improve the efficacy of BMSCs treatment in these patients is to enhance their homing efficiency to the target sites. Studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays an important role in promoting BMSCs homing. In this study, human BMSCs were transduced with lentivirus stably expressing CXCR4-BMSCs. Transduced BMSCs resemble normal BMSCs in many ways. Migration ability of CXCR4-BMSCs toward SDF-1 was increased because of the overexpression of CXCR4. In the mice with bone marrow failure, the migration and colonization ability of CXCR4-BMSCs to the bone marrow was significantly improved as seen by IVIS imaging and FACS. The SDF-1 level in the bone marrow failure mice was significantly higher than in the normal mice. Thus, from our study, it is clear that after CXCR4-BMSCs were infused into mice with bone marrow failure, SDF-1 interacted with CXCR4 receptor, leading cells to migrate and colonize to bone marrow. Because of the high SDF-1 expression in mouse bone marrow and CXCR4 receptor expression in cells, BMSCs homing was increased.
机译：再生障碍性贫血（AA）是一种骨髓衰竭疾病。AA很难治疗，而且由于其复杂的发病机制，复发也很常见。异基因骨髓间充质干细胞（BMSCs）输注是AA患者有效且安全的治疗选择。然而，研究发现，在AA患者中输注BMSCs的有效率不到30%。因此，提高骨髓间充质干细胞治疗效果的关键是提高其对靶点的归巢效率。研究表明，基质细胞衍生因子-1（SDF-1）/CXC趋化因子受体4（CXCR4）轴在促进骨髓间充质干细胞归巢中起重要作用。在本研究中，用稳定表达CXCR4 BMSCs的慢病毒转导人BMSCs。转导的骨髓基质细胞在许多方面与正常的骨髓基质细胞相似。由于CXCR4的过度表达，CXCR4 BMSCs向SDF-1的迁移能力增强。在骨髓衰竭小鼠中，通过IVIS成像和FACS观察，CXCR4 BMSCs向骨髓的迁移和定植能力显著提高。骨髓衰竭小鼠的SDF-1水平显著高于正常小鼠。因此，我们的研究表明，将CXCR4 BMSCs注入骨髓衰竭小鼠后，SDF-1与CXCR4受体相互作用，导致细胞迁移并定植到骨髓中。由于小鼠骨髓中SDF-1的高表达和细胞中CXCR4受体的表达，BMSCs归巢增加。

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