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释放神经营养外泌体以促进中枢神经可塑性的生物活性脊髓支架

Bioactive Spinal Cord Scaffold Releasing Neurotrophic Exosomes to Promote Centralis Neuroplasticity.

作者信息

Mi Sisi, Chang Zhuo, Wang Xue, Gao Jiaxin, Liu Yu, Liu Wenjia, He Wangxiao, Qi Zhongquan

机构信息

Medical College, Guangxi University, Nanning, Guangxi 530004, China.

Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

出版信息

ACS Appl Mater Interfaces. 2023 Apr 5;15(13):16355-16368. doi: 10.1021/acsami.2c19607. Epub 2023 Mar 23.

Abstract

Spinal cord injury (SCI), one of the most serious injuries of the central nervous system, causes physical functional dysfunction and even paralysis in millions of patients. As a matter of necessity, redressing the neuroleptic pathologic microenvironment to a neurotrophic microenvironment is essential in order to alleviate this dilemma and facilitate the recovery of the spinal cord. Herein, based on cell-sheet technology, two functional cell types─uninduced and neural-induced stem cells from human exfoliated deciduous teeth─were formed into a composite membrane that subsequently self-assembled to form a bioactive scaffold with a spinal-cord-like structure, called a spinal cord assembly (SCA). In a stable extracellular matrix microenvironment, SCA continuously released SCA-derived exosomes containing various neurotrophic factors, which effectively promoted neuronal regeneration, axonal extension, and angiogenesis and inhibited glial scar generation in a rat model of SCI. Neurotrophic exosomes significantly improved the pathological microenvironment and promoted centralis neuroplasticity, ultimately eliciting a strong repair effect in this model. SCA therapy is a promising strategy for the effective treatment of SCI based on neurotrophic exosome delivery.

摘要

脊髓损伤(SCI)是中枢神经系统最严重的损伤之一,导致数百万患者出现身体功能障碍甚至瘫痪。为缓解这一困境并促进脊髓恢复,将神经抑制性病理微环境纠正为神经营养性微环境是必要的。在此,基于细胞片技术,两种功能性细胞类型——来自人脱落乳牙的未诱导干细胞和神经诱导干细胞——形成复合膜,随后自组装形成具有脊髓样结构的生物活性支架,称为脊髓组装体(SCA)。在稳定的细胞外基质微环境中,SCA持续释放含有多种神经营养因子的SCA衍生外泌体,在大鼠SCI模型中有效促进神经元再生、轴突延伸和血管生成,并抑制胶质瘢痕形成。神经营养性外泌体显著改善病理微环境并促进中枢神经可塑性,最终在该模型中产生强大的修复作用。基于神经营养性外泌体递送的SCA疗法是有效治疗SCI的一种有前景的策略。

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