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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
- Source :
- Neurochirurgie. 68:188-195
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
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.
- Subjects :
- Central nervous system
Notch signaling pathway
OLIG2
Mice
Myelin
medicine
Animals
Humans
Induced pluripotent stem cell
Spinal Cord Injuries
Oligodendrocyte Precursor Cells
business.industry
Cell Differentiation
Rats
Transplantation
Oligodendroglia
stomatognathic diseases
medicine.anatomical_structure
Spinal Cord
nervous system
NUMB
Cancer research
Surgery
Neurology (clinical)
business
Immunostaining
Signal Transduction
Subjects
Details
- ISSN :
- 00283770
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Neurochirurgie
- Accession number :
- edsair.doi.dedup.....31bd8fc788fa6adf7fa406d4ce3c0da5