Abstract
Background
Neural stem/progenitor cell (NSPC) transplantation in spinal cord injury (SCI) is a potential treatment that supports regeneration by promoting neuroprotection, remyelination, and neurite outgrowth. However, glial scarring hinders neuroregeneration and reduces the efficiency of cell transplantation. The present study aimed to enhance this neuroregeneration by surgically removing the glial scar and transplanting heat-shock (HS) preconditioned NSPCs in combination with Arg-Gly-Asp (RGD)-functionalised hydrogel in a rat spinal cord hemi-transection model.
Methods
Twelve Sprague-Dawley rats underwent spinal cord hemi-transection and were randomly divided into three treatment groups: hydrogel implantation (control group), NSPC-encapsulated hydrogel implantation, and HS-NSPC-encapsulated hydrogel implantation. HS preconditioning was applied to the NSPCs to reinforce cell retention and an RGD-functionalised hydrogel was used as a biomatrix.
Results
In vitro culture showed that preconditioned NSPCs highly differentiated into neurons and oligodendrocytes and exhibited higher proliferation and neurite outgrowth in hydrogels. Rats in the HS-NSPC-encapsulated hydrogel implantation group showed significantly improved functional recovery, neuronal and oligodendrocyte differentiation of transplanted cells, remyelination, and low fibrotic scar formation.
Conclusions
The surgical removal of the glial scar in combination with HS-preconditioning and RGD-functionalised hydrogels should be considered as a new paradigm in NSPC transplantation for spinal cord regeneration treatment.
Graphical Abstract
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Data Availability
All data generated or analysed during this study are included in this published article.
Abbreviations
- 3D :
-
Three dimensional
- BBB :
-
Basso, Beattie, Bresnahan Locomotor Rating Scale
- BDNF :
-
Brain-derived neurotrophic factor
- CNS :
-
Central nervous system
- CXCR4 :
-
C-X-C chemokine receptor type 4
- DAPI :
-
4,6-diamidino-2-phenylindole
- FBS :
-
Fetal bovine serum
- ECM :
-
Extracellular matrix
- GAPHD :
-
Glyceraldehyde-3-phosphate dehydrogenase
- GFAP :
-
Glial fibrillary acidic protein
- HG :
-
Hydrogel
- HS :
-
Heat-shock
- HSP27 :
-
Heat-shock protein 70
- HSP70 :
-
Heat-shock protein 70
- LFB :
-
Luxol fast blue
- MBP :
-
Myelin basic protein
- NGF :
-
Nerve growth factor
- NSPC :
-
Neural stem/progenitor cell
- NSC :
-
Neural stem cells
- OCT :
-
Optimal cutting temperature compound
- PBS :
-
Phosphate-buffered saline
- PFA :
-
Paraformaldehyde
- PLO :
-
Poly-L-ornithine solution
- RGD :
-
Arg-Gly-Asp
- RT :
-
Room temperature
- RT-PCR :
-
Real-time polymerase chain reaction
- SCI :
-
Spinal cord injury
- SOX2 :
-
Sex determining region Y-box 2
- VEGF :
-
Vascular endothelial growth factor
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This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (No. 2018R1D1A1B07047451). The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
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WKK was involved in study design and performed experiments, data analysis, and manuscript writing. BJK were involved in study design and revised the manuscript. All authors read and approved the manuscript.
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The study was approved by the Animal Care and Use Committee of Seoul National University (SNU-220103-6-1; Title: Development of spinal cord injury treatment using neural stem/progenitor cells; Date of approval: April 13, 2022).
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Kim, W.K., Kang, BJ. Transplantation of Heat-Shock Preconditioned Neural Stem/Progenitor Cells Combined with RGD-Functionalised Hydrogel Promotes Spinal Cord Functional Recovery in a Rat Hemi-Transection Model. Stem Cell Rev and Rep 20, 283–300 (2024). https://doi.org/10.1007/s12015-023-10637-8
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DOI: https://doi.org/10.1007/s12015-023-10637-8