Effect of modulating macrophage phenotype on peripheral nerve repair.
Effect of modulating macrophage phenotype on peripheral nerve repair.
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DOI：
10.1016/j.biomaterials.2012.08.050
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发表时间：
2012-12
期刊：
影响因子：
14
通讯作者：
Bellamkonda RV
中科院分区：
文献类型：
--
作者：
Mokarram N;Merchant A;Mukhatyar V;Patel G;Bellamkonda RV
尽管自体移植物移植取得了进展，但周围神经跨越长间隙的修复在临床上仍然具有挑战性。虽然目前已经设计了含有营养因子和细胞外基质分子的支架，但与自体移植物诱导修复的性能相匹配一直是一个挑战。在这项研究中，我们探讨了细胞因子介导的巨噬细胞表型“偏偏”对体外和体内雪旺细胞（SC）迁移和轴突再生的影响。巨噬细胞表型通过在聚合神经引导通道内局部递送干扰素-γ (IFN-γ)或白细胞介素-4 （IL-4）成功调节，使它们分别极化为促炎（M1）或促愈合（M2a和M2c）表型。在一个临界大小的大鼠坐骨神经间隙模型（15 mm）中，巨噬细胞向M2a和M2c表型的初始极化导致SC浸润增强，轴突生长明显加快。巨噬细胞（CD206+/CCR7+）的促愈合与促炎症的比例，定义为再生偏向，与神经支架远端轴突的数量呈线性关系。目前的结果清楚地表明，不是巨噬细胞存在的程度，而是巨噬细胞在损伤部位的特定表型调节再生结果。
Peripheral nerve repair across long gaps remains clinically challenging despite progress made with autograft transplantation. While scaffolds that present trophic factors and extracellular matrix molecules have been designed, matching the performance of autograft-induced repair has been challenging. In this study, we explored the effect of cytokine mediated ‘biasing’ of macrophage phenotypes on Schwann cell (SC) migration and axonal regeneration in vitro and in vivo. Macrophage phenotype was successfully modulated by local delivery of either Interferon-gamma (IFN-γ) or Interleukin-4 (IL-4) within polymeric nerve guidance channels, polarizing them toward pro-inflammatory (M1) or pro-healing (M2a and M2c) phenotypes, respectively. The initial polarization of macrophages to M2a and M2c phenotype results in enhanced SC infiltration and substantially faster axonal growth in a critically-sized rat sciatic nerve gap model (15 mm). The ratio of pro-healing to pro-inflammatory population of macrophages (CD206+/CCR7+), defined as regenerative bias, demonstrates a linear relationship with the number of axons at the distal end of the nerve scaffolds. The present results clearly suggest that rather than the extent of macrophage presence, their specific phenotype at the site of injury regulates the regenerative outcomes.
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影响因子：
2.5
作者：
English, Arthur W.;Chen, Yi;Chen, Xiang Yang
通讯作者：
Chen, Xiang Yang
DOI：
10.1073/pnas.85.5.1701
发表时间：
1988-03-01
影响因子：
11.1
作者：
BAICHWAL, RR;BIGBEE, JW;DEVRIES, GH
通讯作者：
DEVRIES, GH
DOI：
10.1523/jneurosci.3992-08.2009
发表时间：
2009-03-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gensel JC;Nakamura S;Guan Z;van Rooijen N;Ankeny DP;Popovich PG
通讯作者：
Popovich PG
影响因子：
14
作者：
Brown, Bryan N.;Valentin, Jolene E.;Stewart-Akers, Ann M.;McCabe, George P.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
5.3
作者：
Gris, D;Marsh, DR;Weaver, LC
通讯作者：
Weaver, LC