Transplantation of CXCR4 Overexpressed Mesenchymal Stem Cells Augments Regeneration in Degenerated Intervertebral Discs
Transplantation of CXCR4 Overexpressed Mesenchymal Stem Cells Augments Regeneration in Degenerated Intervertebral Discs
复制标题
CXCR4 过表达间充质干细胞的移植可增强退变椎间盘的再生。
DOI：
10.1089/dna.2015.3118
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发表时间：
2016-05-01
影响因子：
3.1
通讯作者：
Tang, Wen-Hao
中科院分区：
文献类型：
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作者：
Wei, Ji-Nan;Cai, Feng;Tang, Wen-Hao
SDF-1/CXCR4趋化信号在调节干细胞组织再生中发挥重要作用。本研究的目的是评估CXCR4的高表达是否增强间充质干细胞（MSC）的迁移并提高椎间盘（IVD）再生的效率。通过慢病毒-CXCR4-vect转染产生过表达CXCR的MSC（CXCR4-MSC），用SPIO标记，并移植到瓣环穿刺诱导的兔退行性IVD中。在移植后 0、8 和 16 周获得脊柱的 X 射线和 T2 加权 MR 图像。通过磁共振成像和普鲁士蓝染色来追踪移植的干细胞。通过量化聚集蛋白聚糖和 II 型胶原蛋白的表达来评估基于干细胞的 IVD 变性。进行体外趋化性测试以研究CXCR4-MSCs向补充SDF-1的迁移。 CXCR4过表达的MSC稳定地升高了CXCR4的表达并增加了向SDF-1的迁移。 SPIO 标记的 CXCR4-MSC 可以在移植后 16 周通过 MRI 在 IVD 内检测到。普鲁士蓝染色证明移植有 CXCR4-MSC 的 IVD 中有更多 SPIO 阳性细胞。与对照组相比，间充质干细胞移植后，椎间盘高度下降速度减慢，聚集蛋白聚糖和 II 型胶原蛋白的 mRNA 表达增加，尤其是在补充 CXCR4-MSC 的 IVD 中。 CXCR4 过表达促进 MSC 在 IVD 内保留并增强基于干细胞的 IVD 再生。 SDF-1/CXCR4 趋化信号可能有助于为理解退化 IVD 内干细胞迁移和浸润提供新的视角。
SDF-1/CXCR4 chemotaxis signals play important roles in regulating the stem cell-based tissue regeneration. The aim of this research is to evaluate whether high expression of CXCR4 enhances the migration of mesenchymal stem cells (MSCs) and increases the efficiency of intervertebral disc (IVD) regeneration. MSCs overexpressing CXCR (CXCR4-MSC) were created by lentiviral-CXCR4-vect transfection, labeled with SPIO, and transplanted into rabbit degenerative IVD induced by annulus puncture. X-ray and T2-weighted MR images of the spine were obtained at 0, 8, and 16 weeks post-transplantation. The transplanted stem cells were traced by both MR imaging and Prussian blue staining. The stem cell-based IVD degeneration was evaluated by quantifying the expression of aggrecan and type II collagen. The in vitro chemotaxis test was performed to study the migration of CXCR4-MSCs to the supplement of SDF-1. The CXCR4-overexpressing MSCs stably elevated the expression of CXCR4 and increased the migration to SDF-1. The SPIO-labeled CXCR4-MSC could be detected within the IVD by MRI till 16 weeks post-transplantation. Prussian blue staining evidenced more SPIO-positive cells within the IVD transplanted with CXCR4-MSCs. Compared to the control group, loss of disc height was slowed while the mRNA expression of aggrecan and type II collagen was increased by MSC transplantation, especially in the IVD supplemented with CXCR4-MSCs. CXCR4 overexpression promoted MSC retention within the IVD and enhanced the stem cell-based IVD regeneration. The SDF-1/CXCR4 chemotaxis signals might help provide a new perspective to understand stem cell migration and infiltration within the degenerated IVD.