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·인용수 14
·2022
Nanogel-mediated delivery of oncomodulin secreted from regeneration-associated macrophages promotes sensory axon regeneration in the spinal cord
Min Kwon, Yeo‐Jin Seo, Hana Cho, Hyung Soon Kim, Young Joo Oh, Simay Genişcan, Minjae Kim, Hee Hwan Park, Eun-hye Joe, Myung‐Hee Kwon, Han Chang Kang, Byung Gon Kim
IF 13.3Theranostics
초록

Preconditioning nerve injury enhances axonal regeneration of dorsal root ganglia (DRG) neurons in part by driving pro-regenerative perineuronal macrophage activation. How these macrophages influence the neuronal capacity of axon regeneration remains elusive. We report that oncomodulin (ONCM) is produced from the regeneration-associated macrophages and strongly influences regeneration of DRG sensory axons. We also attempted to promote sensory axon regeneration by nanogel-mediated delivery of ONCM to DRGs. <b>Methods:</b><i>In vitro</i> neuron-macrophage interaction model and preconditioning sciatic nerve injury were used to verify the necessity of ONCM in preconditioning injury-induced neurite outgrowth. We developed a nanogel-mediated delivery system in which electrostatic encapsulation of ONCM by a reducible epsilon-poly(<sub>L</sub>-lysine)-nanogel (REPL-NG) enabled a controlled release of ONCM. <b>Results:</b> Sciatic nerve injury upregulated ONCM in DRG macrophages. ONCM in macrophages was necessary to produce pro-regenerative macrophages in the <i>in vitro</i> model of neuron-macrophage interaction and played an essential role in preconditioning-induced neurite outgrowth. ONCM increased neurite outgrowth in cultured DRG neurons by activating a distinct gene set, particularly neuropeptide-related genes. Increasing extracellularly secreted ONCM in DRGs sufficiently enhanced the capacity of neurite outgrowth. Intraganglionic injection of REPL-NG/ONCM complex allowed sustained ONCM activity in DRG tissue and achieved a remarkable long-range regeneration of dorsal column sensory axons beyond spinal cord lesion. <b>Conclusion:</b> NG-mediated ONCM delivery could be exploited as a therapeutic strategy for promoting sensory axon regeneration following spinal cord injury.

키워드
NeuriteRegeneration (biology)Sciatic nerveAxonSpinal cordNanogelSpinal cord injuryNerve injurySensory neuronNeuroscience
타입
article
IF / 인용수
13.3 / 14
게재 연도
2022