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

Bioactive Materials, 2023 · DOI: https://doi.org/10.1016/j.bioactmat.2023.06.019 · Published: June 28, 2023

Simple Explanation

This study investigates the potential of spinal cord-derived microvascular endothelial cells (SCMECs) to repair spinal cord injuries (SCI). The research compares SCMECs to brain-derived MECs (BMECs) in terms of their ability to promote blood vessel formation and nerve regeneration after SCI. The study found that SCMECs and BMECs exhibit different gene and protein expression profiles, which are involved in angiogenesis, immunity and metabolism. Also, SCMECs and BMECs could acquire the angiogenic phenotype in response to specific elastic modulus of hydrogels and promoted the proliferation, migration, and neural differentiation. SCMECs combined with a NeuroRegen scaffold showed higher effectiveness than BMECs in promoting vascular reconstruction and nerve regeneration in a rat model of SCI. The potential mechanism involves the VEGF/AKT/eNOS signaling pathway.

Study Duration

8 weeks

Participants

Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
SCMECs and BMECs exhibit distinct gene and protein expression profiles related to angiogenesis, immunity, and metabolism.
2
SCMECs and BMECs promote angiogenesis, proliferation, migration, and neural differentiation, but respond to different stiffness stimulations of PEG hydrogels.
3
SCMECs combined with the NeuroRegen scaffold show higher effectiveness in vascular reconstruction and functional recovery in a rat SCI model, potentially through the VEGF/AKT/eNOS signaling pathway.

Research Summary

This study aimed to uncover the different effects of CNS- derived MECs on SCI repair, particularly on regulating neovascularization and neuroregeneration through systematically comparing the characteristics of SCMECs and BMECs and examining their interactions with SNSCs and BNSCs, respectively. The NeuroRegen scaffold was developed in our laboratory and used together with stem cells in clinical trials, successfully promoting autonomic neural function recovery, increases sensation level, and improves locomotor activity in patients with SCI. In a complete SCI rat model, SCMEC-laden NeuroRegen scaffold significantly improved vascular reconstruction, synergistically accelerating neuronal regeneration and functional recovery compared to BMEC-loaded NeuroRegen scaffold implantation.

Practical Implications

Therapeutic Potential

SCMECs hold promise as a therapeutic approach for restoring vascularization and neural regeneration in SCI.

Scaffold-based delivery

Delivery of SCMECs using the NeuroRegen scaffold enhances cell retention and promotes tissue repair.

Signaling Pathway Target

The VEGF/AKT/eNOS signaling pathway is a potential therapeutic target for promoting angiogenesis and neuronal regeneration in SCI.

Study Limitations

1
The study is limited to a rat model of complete SCI.
2
Further research is needed to translate these findings to human clinical trials.
3
The precise mechanisms underlying the superior effects of SCMECs compared to BMECs require further investigation.

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