源自脊髓的微血管内皮细胞促进脊髓损伤修复。

Microvascular endothelial cells derived from spinal cord promote spinal cord injury repair.

作者信息

You Zhifeng, Gao Xu, Kang Xinyi, Yang Wen, Xiong Tiandi, Li Yue, Wei Feng, Zhuang Yan, Zhang Ting, Sun Yifu, Shen He, Dai Jianwu

机构信息

Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.

出版信息

Bioact Mater. 2023 Jun 28;29:36-49. doi: 10.1016/j.bioactmat.2023.06.019. eCollection 2023 Nov.

DOI:10.1016/j.bioactmat.2023.06.019

PMID:37621772

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10444976/

Abstract

Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.

摘要

脊髓损伤（SCI）后的神经再生与微血管内皮细胞（MEC）介导的神经血管单元形成密切相关。然而，中枢神经系统来源的MEC对新生血管形成和神经发生的影响以及其中涉及的潜在信号尚不清楚。在此，我们建立了一种高细胞产量和纯度的原发性脊髓来源的MEC（SCMEC）分离方法，以描述其与脑来源的MEC（BMEC）的差异及其对SCI的治疗作用。转录组学和蛋白质组学显示，SCMEC中差异表达的基因和蛋白质参与血管生成、免疫、代谢，并且细胞粘附分子信号是差异表达基因和蛋白质KEGG分析中富集的前10条信号通路中的唯一信号通路。SCMEC和BMEC可以分别通过聚乙二醇水凝胶的不同硬度刺激诱导血管生成，弹性模量分别为50-1650 Pa（针对SCMEC）和50-300 Pa（针对BMEC）。此外，SCMEC和BMEC在不同水平上促进脊髓或脑来源的神经干细胞（SNSC/BNSC）的增殖、迁移和分化。在一定剂量下，SCMEC与NeuroRegen支架联合使用时，在促进血管重建方面显示出更高的有效性。这种现象的潜在机制可能是通过VEGF/AKT/eNOS信号通路，因此与BMEC相比，加速了SCI大鼠的神经元再生和功能恢复。我们的研究结果表明SCMEC在恢复血管化和神经再生方面具有广阔前景。