Stem Cell Scaffolds for the Treatment of Spinal Cord Injury—A Review
Abstract
:1. Introduction
2. NSC Differentiation
2.1. Notch Signaling in NSC Differentiation
2.2. Wnt/β-Catenin Signaling in NSC Differentiation
2.3. Shh Signaling in NSC Differentiation
2.4. BMP Signaling in NSC Differentiation
3. Substrates Indicated for Axonal Regrowth Post-Injury
3.1. Plasma Membrane Sealants
3.2. Growth Cone Formation and Stability
3.3. Neurotrophic Factors and Guidance
3.4. Matrix Vehicles for Axonal Regeneration
3.5. Electrical Stimulation for Axonal Growth
4. Overview of Stem Cell Scaffolding
4.1. Natural Polymer Scaffolds
4.2. Synthetic Polymer Scaffolds
4.3. Hydrogel Scaffolds
4.4. Hybrid or Composite Scaffolds
4.5. Growth Modulating Factors
5. Emerging Pre-Clinical Studies and Their Applications for Clinical Adoption
6. Conclusions and Future Research Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
3D | Three dimensional |
AIS | American Spinal Injury Association Impairment Scale |
BDNF | Brain-derived neurotrophic factor |
BMP | Bone morphogenetic protein |
CNS | Central nervous system |
CSF | Cerebrospinal fluid |
ES | Electrical stimulation |
GDNF | Glial cell line-derived neurotrophic factor |
GFAP | Glial fibrillary acidic protein |
GSK-3β | Glycogen-synthase-kinase-3β |
GelMA | Gelatin methacryloyl |
IMLL | Intramedullary lesion length |
MAPK | Mitogenactivated protein kinase |
MP | Methylprednisolone |
MRI | Magnetic resonance imaging |
MSC | Mesenchymal stem cell |
MenSCs | Menstrual blood-derived mesenchymal stem cells |
NCID | Notch intracellular signaling domain |
NF-L | Neurofilament light |
NGF | Nerve growth factor |
NSC | Neural stem cell |
NSPCs | Neural stem progenitor cells |
NT3 | Neurotrophin-3 (NT3) |
PI3K | Phosphatidylinositol 3-kinase |
RAG | Recombination activating gene |
SCI | Spinal cord injury |
Shh | Sonic hedgehog |
VEGF | Vascular endothelial growth factor |
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Source | Subject | Stem Cell Type | Scaffold Material | Outcome |
---|---|---|---|---|
Kourgiantaki et al. [129] | C57/BL6 mice | NSPCs | Collagen | Improved axonal elongation, neural regeneration at SCI lesions, enhanced NSPC differentiation, and functional integration of the regenerated cells into the preexisting neural network |
Liu et al. [131] | Sprague-Dawley rats | NSCs | Collagen | Improved hindlimb motor function, nerve regeneration, and neural cell extension |
Deng et al. [130] | Sprague-Dawley rats and beagle canines | MSCs | Collagen | Increased motor scores, reduced SCI lesions |
Deng et al. [130] | Humans | MSCs | Collagen | Emergence of novel nerve fiber growth, improved electrophysiological activity of neurons adjacent to the SCI lesion, increased daily life scores, increased American Spinal Injury Association scores, improved bladder and bowel functioning |
Tang et al. [109] | Humans | Bone marrow mononuclear cells and MSCs | Collagen | Improved bowel and bladder sensation, improved voluntary walking activity, enhanced finger mobility |
Liu et al. [128] | Sprague-Dawley rats | NSPCs | Collagen modified with N-cadherin | Increased NSPC recruitment to SCI lesion, improved locomotor activity |
Chen et al. [135] | Sprague-Dawley rats | MSCs | Collagen modified with silk | Improved nerve fiber regeneration, enhanced remyelination, establishment of novel synaptic connections at the SCI lesion |
Deng et al. [132] | Beagle canines | MSCs | Collagen modified with heparan sulfate | Improved locomotor activity, improved urodynamic parameters, modulation of cytokines |
Source | Subject | Stem Cell Type | Scaffold Material | Outcome |
---|---|---|---|---|
Wang et al. [144] | Sprague-Dawley rats | NSCs | Matrigel | Slight neural recovery and improved motor function |
Li et al. [142] | Sprague-Dawley rats | MSCs | Hyaluronic acid hydrogel with manganese dioxide nanoparticles | Enhanced MSC growth and differentiation, restoration of locomotor function |
Abdolahi et al. [140] | Sprague-Dawley rats | NSCs | PuraMatrix peptide hydrogel | Enhance NSC survival and differentiation, reduced SCI lesion volume, improved neurologic functioning |
Yang et al. [143] | C57/BL6 mice | NSPCs | Hydrogel enhanced with agarose, gelatin, and polypyrrole | Enhanced NSPC differentiation, reduced SCI lesion volume |
He et al. [138] | Sprague-Dawley rats | MenSCs | DSCG/GelMA hydrogel | Improved motor function, reduced inflammation, enhanced MenSC differentiation |
Cai et al. [139] | Sprague-Dawley rats | NSCs | GelMA-MXene hydrogel | Improved motor function, reduced inflammation, enhanced NSC differentiation |
Shen et al. [141] | C57/BL6 mice | NSCs | IL-10-enhanced hydrogel | Enhanced NSC differentiation, neural regeneration, and axonal regrowth |
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Hey, G.; Willman, M.; Patel, A.; Goutnik, M.; Willman, J.; Lucke-Wold, B. Stem Cell Scaffolds for the Treatment of Spinal Cord Injury—A Review. Biomechanics 2023, 3, 322-342. https://doi.org/10.3390/biomechanics3030028
Hey G, Willman M, Patel A, Goutnik M, Willman J, Lucke-Wold B. Stem Cell Scaffolds for the Treatment of Spinal Cord Injury—A Review. Biomechanics. 2023; 3(3):322-342. https://doi.org/10.3390/biomechanics3030028
Chicago/Turabian StyleHey, Grace, Matthew Willman, Aashay Patel, Michael Goutnik, Jonathan Willman, and Brandon Lucke-Wold. 2023. "Stem Cell Scaffolds for the Treatment of Spinal Cord Injury—A Review" Biomechanics 3, no. 3: 322-342. https://doi.org/10.3390/biomechanics3030028