A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in the Notch signaling pathway

H Yuan; C-L Fang; Y-P Deng; J Huang; R-Z Niu; J-L Chen; T-B Chen; Z-Q Zhu; L Chen; L-L Xiong; T-H Wang

doi:10.1016/j.neuchi.2021.09.004

A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in the Notch signaling pathway

Neurochirurgie. 2022 Feb;68(2):188-195. doi: 10.1016/j.neuchi.2021.09.004. Epub 2021 Sep 17.

Authors

H Yuan¹, C-L Fang², Y-P Deng³, J Huang⁴, R-Z Niu⁵, J-L Chen⁵, T-B Chen⁵, Z-Q Zhu⁶, L Chen⁷, L-L Xiong⁶, T-H Wang⁸

Affiliations

¹ Institute of Neuroscience, Kunming Medical University, Kunming 650031, Yunnan, China; Department of Spine Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China.
² Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Department of Anesthesiology, National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan, China.
³ Department of Anesthesiology, National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan, China.
⁴ Institute of Neuroscience, Kunming Medical University, Kunming 650031, Yunnan, China.
⁵ Laboratory Animal Department, Kunming Medical University, Kunming 650031, Yunnan, China.
⁶ Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China.
⁷ Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
⁸ Institute of Neuroscience, Kunming Medical University, Kunming 650031, Yunnan, China; Laboratory Animal Department, Kunming Medical University, Kunming 650031, Yunnan, China; Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: Wangth_email@163.com.

PMID: 34543615
DOI: 10.1016/j.neuchi.2021.09.004

Abstract

Background: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation.

Methods: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation.

Results: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation.

Conclusions: A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.

Keywords: A2B5+ OPC transplantation; Motor and sensory function; Notch signaling pathway; Spinal cord contusion.

MeSH terms

Animals
Cell Differentiation
Humans
Mice
Oligodendrocyte Precursor Cells* / transplantation
Oligodendroglia
Rats
Signal Transduction
Spinal Cord
Spinal Cord Injuries* / surgery