A cryo-shocked M2 macrophages based treatment strategy promoting repair of spinal cord injury via immunomodulation and axonal regeneration effects.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Ermei Lu, Kecheng Zhou, Jiansen Miao, Yanlin Zhu, Jiyao Tang, Siting Du, Yanzhen Feng, Linyuan Jiang, Tianyao Jiang, Ting Huang, Ping Li, Xinjun Miao, Qi Han, Jian Xiao
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Abstract

Recovery from spinal cord injury (SCI) is often impeded by neuroinflammation, scar formation, and limited axonal regeneration. To tackle these issues, we developed an innovative biomimetic drug delivery system using liquid nitrogen-treated M2 macrophages (LNT M2) which internalized paclitaxel (PTX) nanoparticles beforehand. These were incorporated into a gelatin methacryloyl (GelMA) scaffold, creating a multifunctional, injectable treatment for single-dose administration. The LNT M2 inherited the inflammatory factor/chemokine receptors from the living M2 macrophages and thus possessing significant inflammatory neutralizing effect. In addition, the scaffold provides slow, sustained release of PTX, promoting axonal regeneration and suppressing scar formation in SCI rats. The LNT M2-based dual-functional scaffold significantly enhances motor function, reduces neuroinflammation, and accelerates axonal regeneration by modulating the inflammatory microenvironment and preventing the formation of glial and fibrotic scars. This approach combines the regenerative effects of low-dose PTX with the immunoregulatory properties of LNT M2, leading to remarkable neurological recovery in SCI rats. Moreover, the scaffold's straightforward preparation, ease of standardization, and "ready-to-use" nature make it a promising candidate for acute SCI intervention and future clinical applications.

基于冷休克M2巨噬细胞的治疗策略通过免疫调节和轴突再生作用促进脊髓损伤修复。
脊髓损伤(SCI)的恢复常常受到神经炎症、瘢痕形成和轴突再生受限的阻碍。为了解决这些问题,我们开发了一种创新的仿生给药系统,使用液氮处理的M2巨噬细胞(LNT M2)预先内化紫杉醇(PTX)纳米颗粒。这些被纳入明胶甲基丙烯酰(GelMA)支架,创造多功能,单剂量注射治疗。LNT M2继承了活的M2巨噬细胞的炎症因子/趋化因子受体,具有显著的炎症中和作用。此外,该支架能缓慢、持续地释放PTX,促进脊髓损伤大鼠轴突再生,抑制瘢痕形成。基于LNT m2的双功能支架通过调节炎症微环境,防止胶质瘢痕和纤维化瘢痕的形成,显著增强运动功能,减少神经炎症,加速轴突再生。该方法将低剂量PTX的再生作用与LNT M2的免疫调节特性结合起来,导致脊髓损伤大鼠的神经功能显著恢复。此外,该支架的制备简单、易于标准化和“即用”的性质使其成为急性SCI干预和未来临床应用的有希望的候选者。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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索莱宝
inflammatory/chemotactic factors ELISA kits
索莱宝
coomassie brilliant blue staining
阿拉丁
Paclitaxel
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