Table 2.
Preclinical studies using neural stem cells transplantation to target spinal cord injury repair.
| SCI | Animal Model | Injury | Transplanted Cells | Time | Additional Treatments | Outcomes | REF |
|---|---|---|---|---|---|---|---|
| Transection | Fischer 344 Rat C57BL/6 Mice |
T3 C4 |
Rat E14 SC-derived NPCs Mouse E12 SC-derived cells |
2 w | Cell grafts survival Full-fill of the cavitation site Axonal CST regeneration and functional synaptic formation Improved forelimb function |
[144] | |
| Contusion | C57BL/6 Mice | T9/10 | Mouse Fetal Brain NSCs | 1 w | Migration from the injection site toward the injury Locomotor improvement Reduction in neutrophils and iNOS+/Mac-2+ cells Downregulation of TNF-α, IL-1β, IL-6 and IL-12 |
[170] | |
| Hemisection | Fischer 344 Rat | C5 | Rat E14 SC-derived NPCs | 2 w | 4-factor cocktail | Consistent graft survival Neuronal differentiation Reduction of the lesion site |
[145] |
| Compression | Wistar Rat | T10 | Human Fetal Spinal Cord SPC-01 cell line | 1 w | Downregulation of TNF-α Inhibition of p65 NF-κB Reduction of glial scar and cavity size Gray matter preservation |
[147] | |
| Compression | C57BL/6 Mice | T6 | ES-dNSC | 1 w | Enhancement of spared neural tissue Differentiation into oligodendrocytes Motor improvement |
[171] | |
| Hemisection | Nude Rat | C5 | H9 ESC-derived NSCs | 2 w | Graft size stable over time Differentiation into mature neurons and glia Long axonal regrowth Glial migration to host white matter |
[150] | |
| Contusion | NOD-scid Mice | T9 | hCNS-derived NSCs | 0 | Astroglial differentiation of donor cells in the lesion site No locomotor recovery |
[138] | |
| Transection | Nude Rat | C4 | hPSC-derived Spinal Cord NSCs | 2 w | NSCs committed to a spinal cord phenotype Differentiation into excitatory neurons Regeneration of the CST Host-to-graft synaptic connectivity |
[151] | |
| Compression | WT Mouse C3Fe.SWV-Mbpshi/J Mice |
T6 | iPS-derived NSCs | 1 w | Integration within the lesion site Differentiation to oligodendrocytes wt-iPS-dNSCs promote remyelination and axonal function Motor Improvements |
[53] | |
| Compression | Wistar Rat | T8 | iPS-derived NPs | 1 w | Intraspinal implantation promote: > gray and white matter sparing > axonal sprouting > astrogliosis reduction Moderate functional recovery |
[152] | |
| Compression | Wistar Rat | T8/T9 | hiPSC-derived NPs | 1 w | Cell survival and tissue preservation Differentiation into the three germ layers Motor improvement Increased expression of NFs Neuronal regeneration |
[153] | |
| Contusion | C57BL/6 Mice | T10 | iPSC-derived NPCs | 1 w | Neuronal lineage differentiation No tumor formation No locomotor recovery |
[167] | |
| Contusion | Long-Evans hooded Rat | T10 | Human Fetal Brain NSCs | 4 w | Trophic effect in the CSF Motor improvement |
[140] | |
| Contusion | C57BL/6 Mice | T9 | Mouse Striatal NS/PCs | 7–10 d | Treadmill Training | Differentiation into neurons, oligodendrocytes, and astrocytes Electrophysiologic recovery Locomotor improvements |
[141] |
| Contusion | Rat | T10 | Rat Spinal Cord NSCs | 13 w | Ch combined with NFs | 60% of survival < 40% of the lesion site covered Improvement in bladder function |
[172] |
| Hemisection | Tree Shrew | T10 | Shrew Fetal NSCs | 9 d | Self-renewal potential Differentiation into neurons and astrocytes Production of NFs (CNTF, TGF-β1, GDNF, NGF, BDNF and IGF) |
[142] | |
| Contusion | Wistar Rat | C6/C7 | Rat Fetal Brain NSCs | 10 d | Long-term survival Differentiation along the oligodendroglial lineage Reduction in M1 macrophages Lower density of iNOS Functional recovery Reduction in apoptosis |
[143] | |
| Contusion | Sprague–Dawley Rat | T12 | mESC-derived NPCs | 3 w | In vitro differentiation into a spinal GABAergic phenotype Attenuation of chronic neuropathic pain |
[146] | |
| Hemisection | Nude Rat | C5 | Human H9 ESC-derived NSCs | 2 w | No cellular migration Improvement in skilled forelimb motor function |
[149] | |
| Contusion | C57BL/6 Mice | C6/C7 | iPS-derived NSCs | 8 w | Intrathecal ChABC | Cell survival Remyelination and synaptic formation Behavioral recovery of the forelimb grip strength and locomotion |
[27] |
| Contusion | NOD-SCID Mice | T10 | hiPSC-derived NS/PCs | 6 w | GSI | Axonal regrowth and remyelination Reticulo-spinal tract fiber formation Motor functional recovery |
[165] |
| Compression | Wistar Rat | T8/T8 | hiPSC-derived NS/PCs | 5 w | Laminin-coated pHEMA-MOETACl hydrogel | Survival and integration within the lesion spinal cord Reduction in cavity depth and axonal growth Increased number of astrocytes, blood vessels, and TH+ fibers No locomotor recovery |
[166] |
Abbreviations: w weeks; d days; wt wild-type; ChABC chondroitinase ABC; NTFs neurotrophic factors; GSI gamma-secretase inhibitor; CST corticospinal tract; BDNF brain-derived neurotrophic Factor; bFGF basic-fibroblastic growth Factor; VEGF vascular endothelial growth factor; NSC neural stem cell; NPC neural progenitor cell; iPSC-derived NSC induced pluripotent stem cell-derived NSCs; mESC-derived NPCs mouse embryonic stem cell–derived NPCs; hiPSC-derived NS/PCs human induced pluripotent stem cell-derived NS/PCs; ES-dNSC embryonic stem-definitive NSCs; hCNS-derived NSCs human central nervous system-derived NSCs.