Background

Understanding the role of macrophages at discrete spatial locations during nerve regeneration after injury is important. But, methodologies that systemically manipulate macrophages can obscure their roles within discrete spatial locations within nerve.

New method

Liposomes were embedded within fibrin gels to construct a delivery system that facilitated macrophage-specific manipulations at a sole spatial region, as macrophages accumulated within the fibrin. Clodronate liposomes were characterized for their toxicity to specific cells composing nervein vitro, then tested for macrophage-specific depletion in vivo. This delivery system using clodronate liposomes was used to repair a mouse sciatic nerve gap to evaluate its efficacy and effects.

Result

Clodronate liposomes showed specific toxicity to macrophages without affecting dorsal root ganglia (DRG)-derived neurons, endothelial cells, or Schwann cells in culture. The delivery system demonstrated sustained release of liposomes for more than 7 days while still retaining liposomes within the fibrin. In vivo, the delivery system demonstrated macrophages were targeted by liposomes, and the use of clodronate liposomes minimized macrophage accumulation within fibrin, while not affecting macrophage accumulation within DRG. Nerve regeneration across the nerve gap repaired using this delivery system was associated with decreased angiogenesis, Schwann cell accumulation, axon growth, and reinnervation of affected muscle.

Comparison with existing methods

This delivery system allowed specific perturbation of macrophages locally in nerve. This method could be applicable across species without the need for genetic manipulations or systemic pharmaceuticals.

Conclusion

Liposomes embedded within fibrin gels locally target macrophages at the site of nerve injury, which enables greater precision in conclusions regarding their roles in nerve.

中文翻译：

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嵌入纤维蛋白凝胶中的脂质体有助于神经内的局部巨噬细胞操作

背景

了解巨噬细胞在损伤后神经再生过程中离散空间位置的作用很重要。但是，系统地操纵巨噬细胞的方法可能会掩盖它们在神经内离散空间位置中的作用。

新方法

脂质体被嵌入纤维蛋白凝胶中，以构建一个递送系统，该系统在巨噬细胞在纤维蛋白内积累时，促进了巨噬细胞在单个空间区域的特异性操作。氯膦酸盐脂质体在体外对其对构成神经的特定细胞的毒性进行了表征，然后在体内测试了巨噬细胞特异性耗竭。这种使用氯膦酸盐脂质体的递送系统用于修复小鼠坐骨神经间隙，以评估其功效和效果。

结果

氯膦酸盐脂质体对巨噬细胞表现出特异性毒性，而不会影响培养中的背根神经节 (DRG) 衍生的神经元、内皮细胞或雪旺氏细胞。递送系统显示脂质体持续释放超过 7 天，同时仍将脂质体保留在纤维蛋白内。在体内，递送系统证明巨噬细胞被脂质体靶向，氯膦酸盐脂质体的使用最大限度地减少了纤维蛋白内的巨噬细胞积累，同时不影响 DRG 内的巨噬细胞积累。使用这种传递系统修复的跨神经间隙的神经再生与血管生成减少、雪旺细胞积累、轴突生长和受影响肌肉的神经再支配有关。

与现有方法的比较

这种传递系统允许对神经中局部的巨噬细胞进行特定的扰动。这种方法可以跨物种适用，无需基因操作或全身药物。

结论

嵌入纤维蛋白凝胶中的脂质体局部靶向神经损伤部位的巨噬细胞，这使得关于它们在神经中的作用的结论更加精确。