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

被引:24
作者
You, Zhifeng [1 ]
Gao, Xu [1 ,2 ]
Kang, Xinyi [3 ]
Yang, Wen [1 ]
Xiong, Tiandi [1 ,4 ]
Li, Yue [5 ]
Wei, Feng [1 ,4 ]
Zhuang, Yan [1 ,4 ]
Zhang, Ting [5 ]
Sun, Yifu [2 ]
Shen, He [1 ,4 ]
Dai, Jianwu [1 ,6 ]
机构
[1] Chinese Acad Sci, Suzhou Inst Nanotech & Nanobionics, Div Nanobiomedicine, Key Lab Nanobio Interface Res, Suzhou 215123, Peoples R China
[2] Jilin Univ, China Japan Union Hosp, Dept Orthopaed Surg, Changchun 130033, Peoples R China
[3] Soochow Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Suzhou 215004, Peoples R China
[4] Univ Sci & Technol China, Sch Nanotech & Nanobionics, Hefei 230026, Peoples R China
[5] Chinese Acad Sci, Suzhou Inst Nanotech & Nanobionics, Key Lab Multifunct Nanomat & Smart Syst, i Lab, Suzhou 215123, Peoples R China
[6] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China
基金
中国国家自然科学基金;
关键词
Microvascular endothelial cells; Spinal cord injury; NeuroRegen scaffold; Neural regeneration; MESENCHYMAL STEM-CELLS; BARRIER; ANGIOGENESIS; DIFFERENTIATION; SCAFFOLDS; CULTURES; NERVE;
D O I
10.1016/j.bioactmat.2023.06.019
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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.
引用
收藏
页码:36 / 49
页数:14
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