Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2
Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2
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DOI：
10.1016/j.stem.2008.03.003
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发表时间：
2008-06-01
期刊：
影响因子：
23.9
通讯作者：
Braun, Thomas
中科院分区：
文献类型：
--
作者：
Belema-Bedada, Fikru;Uchida, Shizuka;Braun, Thomas
不同来源的循环干细胞已被证明在全身和局部应用后改善各种器官的修复，尽管引起这些作用的机制仍不完全清楚。我们已经使用了DNA微阵列分析和体外迁移试验相结合，以筛选介导长期更新的成人骨髓来源的多能间充质干细胞（BM-MASCs）归巢的分子。我们发现，细胞因子受体CCR 2是骨髓来源的MASCs在转基因小鼠模型中器官特异性归巢到心脏和缺血/再灌注损伤的心脏所必需的。干细胞的归巢和迁移依赖于与CCR 2相互作用的细胞内衔接分子FROUNT。FROUNT是MASC极化所必需的，导致CCR 2聚集和细胞骨架重组。由CCR 2配体MCP-1/CCL 2召集的MASC表达SDF 1，其可能捕获额外的骨髓来源的循环细胞，以促进循环干细胞和祖细胞的归巢和保留的复杂过程，从而重塑患病器官。
Circulating stem cells of different origin have been demonstrated to improve repair of various organs both after systemic and local application, although the mechanisms that cause these effects are still not fully understood. We have used a combination of DNA microarray analysis and in vitro migration assays to screen for molecules that mediate homing of long-term renewing adult bone marrow-derived multipotent mesenchymal stem cells (BM-MASCs). We show that the cytokine receptor CCR2 is necessary for organ-specific homing of bone marrow-derived MASCs to the heart in a transgenic mouse model and into hearts damaged by ischemia/reperfusion. Homing and migration of stem cells was dependent on the intracellular adaptor molecule FROUNT, which interacts with CCR2. FROUNT was required for polarization of MASCs, resulting in clustering of CCR2 and reorganization of the cytoskeleton. Recruited MASCs summoned by the CCR2 ligand MCP-1/CCL2 expressed SDF1, which might trap additional bone marrow-derived circulating cells to contribute to the complex process of homing and retention of circulating stem and progenitor cells to remodel diseased organs.