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鹿茸芽基祖细胞工程化细胞外囊泡：脊髓损伤的一种治疗选择

Engineered Extracellular Vesicles from Antler Blastema Progenitor Cells: A Therapeutic Choice for Spinal Cord Injury.

作者信息

Yang Shijie, Xue Borui, Zhang Yongfeng, Wu Haining, Yu Beibei, Li Shengyou, Ma Teng, Gao Xue, Hao Yiming, Guo Lingli, Liu Qi, Gao Xueli, Yang Yujie, Wang Zhenguo, Qin Mingze, Tian Yunze, Fu Longhui, Zhou Bisheng, Li Luyao, Li Jianzhong, Gong Shouping, Xia Bing, Huang Jinghui

机构信息

Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, P.R. China.

Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an 710004, P.R. China.

出版信息

ACS Nano. 2025 Feb 18;19(6):5995-6013. doi: 10.1021/acsnano.4c10298. Epub 2025 Jan 22.

DOI:10.1021/acsnano.4c10298
PMID:39841785
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11841045/
Abstract

Deer antler blastema progenitor cells (ABPCs) are promising for regenerative medicine due to their role in annual antler regeneration, the only case of complete organ regeneration in mammals. ABPC-derived signals show great potential for promoting regeneration in tissues with limited natural regenerative ability. Our findings demonstrate the capability of extracellular vesicles from ABPCs (EVs) to repair spinal cord injury (SCI), a condition with low regenerative capacity. EVs significantly enhanced the proliferation of neural stem cells (NSCs) and activated neuronal regenerative potential, resulting in a 5.2-fold increase in axonal length. Additionally, EVs exhibited immunomodulatory effects, shifting macrophages from M1 to M2. Engineered with activated cell-penetrating peptides (ACPPs), EVs significantly outperformed EVs from rat bone marrow stem cells (EVs) and neural stem cells (EVs), promoting a 1.3-fold increase in axonal growth, a 30.6% reduction in neuronal apoptosis, and a 2.6-fold improvement in motor function recovery. These findings support ABPC-derived EVs as a promising therapeutic candidate for SCI repair.

摘要

鹿茸芽基祖细胞（ABPCs）因其在每年鹿茸再生中的作用而在再生医学领域具有广阔前景，鹿茸再生是哺乳动物中唯一完全器官再生的案例。ABPCs衍生的信号在促进天然再生能力有限的组织再生方面具有巨大潜力。我们的研究结果证明了ABPCs来源的细胞外囊泡（EVs）修复脊髓损伤（SCI）的能力，脊髓损伤的再生能力较低。EVs显著增强了神经干细胞（NSCs）的增殖并激活了神经元再生潜能，导致轴突长度增加了5.2倍。此外，EVs表现出免疫调节作用，使巨噬细胞从M1型转变为M2型。用活化的细胞穿透肽（ACPPs）进行工程改造后，EVs的表现明显优于大鼠骨髓干细胞来源的EVs和神经干细胞来源的EVs，促进轴突生长增加1.3倍，神经元凋亡减少30.6%，运动功能恢复改善2.6倍。这些研究结果支持ABPCs来源的EVs作为脊髓损伤修复的一种有前景的治疗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a1/11841045/d3be2d3a571c/nn4c10298_0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a1/11841045/d3be2d3a571c/nn4c10298_0007.jpg

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本文引用的文献

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Single-cell and spatial atlases of spinal cord injury in the Tabulae Paralytica.Tabulae Paralytica 脊髓损伤的单细胞和空间图谱。
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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.细胞外囊泡研究的最低信息要求（MISEV2023）：从基础到先进方法。
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Clinical applications of stem cell-derived exosomes.干细胞衍生的外泌体的临床应用。
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Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury.脊髓损伤后，神经元铁稳态的恢复可使神经发生重获活力。
Proc Natl Acad Sci U S A. 2023 Nov 14;120(46):e2220300120. doi: 10.1073/pnas.2220300120. Epub 2023 Nov 10.
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Schwann Cell-Derived Exosomes and Methylprednisolone Composite Patch for Spinal Cord Injury Repair.雪旺细胞衍生外泌体与甲泼尼龙复合贴剂修复脊髓损伤。
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