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

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

doi:10.1016/j.bioactmat.2023.06.019

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

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

Authors

Zhifeng You¹, Xu Gao^{1

2}, Xinyi Kang³, Wen Yang¹, Tiandi Xiong^{1

4}, Yue Li⁵, Feng Wei^{1

4}, Yan Zhuang^{1

4}, Ting Zhang⁵, Yifu Sun², He Shen^{1

4}, Jianwu Dai^{1

6}

Affiliations

¹ 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.
² Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
³ Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
⁴ School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China.
⁵ i-Lab, Key Laboratory of Multifunction Nanomaterials and Smart Systems, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
⁶ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

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.

Keywords: Microvascular endothelial cells; Neural regeneration; NeuroRegen scaffold; Spinal cord injury.