Enhanced Migration of Bone Marrow-Derived Mesenchymal Stem Cells with Tetramethylpyrazine and Its Synergistic Effect on Angiogenesis and Neurogenesis After Cerebral Ischemia in Rats
Enhanced Migration of Bone Marrow-Derived Mesenchymal Stem Cells with Tetramethylpyrazine and Its Synergistic Effect on Angiogenesis and Neurogenesis After Cerebral Ischemia in Rats
复制标题
四甲基吡嗪促进大鼠脑缺血后骨髓间充质干细胞迁移及其对血管生成和神经发生的协同作用
DOI：
10.1089/scd.2018.0254
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发表时间：
2019-07-01
影响因子：
4
通讯作者：
Yin, Yuanjun
中科院分区：
文献类型：
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作者：
Li, Lin;Chu, Lisheng;Yin, Yuanjun
骨髓间充质干细胞（BMSCs）具有分泌多种营养因子的能力，具有血管生成和神经生成的潜能，因此在治疗缺血性卒中方面具有广阔的前景。然而，骨髓间充质干细胞向梗死区域迁移的能力相对较差，限制了治疗中风的有效疗法。骨髓间充质干细胞与药物联合应用可促进骨髓间充质干细胞向梗死区迁移，提高脑卒中后的治疗效果。本研究旨在探讨BMSC联合川芎嗪（TMP）是否能促进BMSC向缺血脑内迁移，从而对脑卒中有更好的治疗效果。在大鼠中风模型中，我们发现联合治疗显著上调缺血性脑基质衍生因子-1（SDF-1）和CXC趋化因子受体4（CXCR 4）的表达，并促进BMSC归巢向缺血区域比BMSC单药治疗。此外，BMSCs联合TMP协同增加血管内皮生长因子和脑源性神经营养因子的表达，促进血管生成和神经发生，改善卒中后的功能结局。这些结果表明，联合治疗不仅可以增强骨髓间充质干细胞迁移到缺血性脑，但也以协同的方式，以加强内源性修复过程和功能恢复缺血性中风后。
Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for treating ischemic stroke owing to their capacity to secrete various trophic factors with potent angiogenic and neurogenic potentials. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limits effective therapies for the treatment of stroke. The combination of BMSCs and pharmacological agent can promote the migration of BMSCs toward infarcted regions and improve the therapeutic effects after stroke. In this study, we aimed to investigate whether BMSCs combined with tetramethylpyrazine (TMP) enhanced BMSC migration into the ischemic brain, which had better therapeutic effect in the treatment of stroke. In a rat stroke model, we found that combination treatment significantly upregulated ischemic brain stromal-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) expressions, and promoted BMSCs homing toward the ischemic regions than BMSC monotherapy. Moreover, BMSCs combined with TMP synergistically increased the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, promoted angiogenesis and neurogenesis, and improved functional outcome after stroke. These results suggest that combination treatment could not only enhance the migration of BMSCs into the ischemic brain but also act in a synergistic way to potentiate endogenous repair processes and functional recovery after ischemic stroke.