Liposomes embedded within fibrin gels facilitate localized macrophage manipulations within nerve
| Autor: | Susan E. Mackinnon, Lauren Schellhardt, Jesús A. Acevedo-Cintrón, Matthew D. Wood, Deng Pan, Alison K. Snyder-Warwick, Junichi Sayanagi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Angiogenesis Schwann cell Fibrin Article 03 medical and health sciences Mice 0302 clinical medicine In vivo medicine Animals Liposome biology Chemistry General Neuroscience Macrophages Endothelial Cells Nerve injury Cell biology 030104 developmental biology medicine.anatomical_structure Liposomes biology.protein Sciatic nerve medicine.symptom Gels 030217 neurology & neurosurgery Reinnervation |
| Zdroj: | J Neurosci Methods |
| ISSN: | 1872-678X |
| Popis: | 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 nerve in 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. |
| Databáze: | OpenAIRE |
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