Review Article

Oligodendrocyte Precursor Cells in Spinal Cord Injury: A Review and Update

Table 1

The summary of OPCs transplantation-associated literatures within the review.

ReferencesCells utilizedIn vivo modelsTransplantation strategiesResults
Time pointQuantityLocation

Cao et al. [34]CNTF-expressing OPCs and regular OPCsContusive spinal cord injury (T9)8 days after injury4 × 1051 mm cranial and caudal to the lesion;
left and right of the lesion
Implanted OPCs develop into mature oligodendrocytes
tcMMEPs and MIER confirm a progressive recovery in both CNTF-expressing and regular OPCs, though it is more significant in the former group

Franklin et al. [35]LacZ labeled CG4 cell lineX-irradiation pretreatment
(T12 to L4)
Ethidium bromide-induced demyelination
Lesion center; adjacent areas; remote areasCells survive, migrate, and are remyelinated better in irradiated cords than nonirradiated cords
In nonirradiated cords, adjacently transplanted cells contribute to remyelination, whereas remotely transplanted cells do not

Lee et al. [36]O-2A cells from P2 rat brainContusive spinal cord injury
(T9)
7 days after injury5 × 105Lesion centerTransplanted cells survive and differentiate into oligodendrocytes but not astrocytes or neurons
A significant improvement in hindlimb performance
There are no differences in SSEPs study, but the latency of MEPs is shorter in transplantation group

Rosenbluth et al. [37]Transgenic mice with LacZ gene under control of MBP promoterContusive spinal cord injury
(T9 to T10)
1 day–16 days after injury1 × 106Lesion centerCells move rostrocaudally over considerable distances and more readily to demyelinated areas
Some of the cells succeed in myelin formation

Bambakidis and Miller [38]OPCs from P0 rat spinal cordsContusive spinal cord injury
(T9 to T10)
5 days after injury1.5 × 105Lesion centerTransplantation of OPCs with or without SHH improves axonal conduction (MEPs) and hindlimbs motor function
The benefits seem more pronounced with the addition of SHH

Sun et al. [39]mESCs-derived OPCsIrradiation spinal cord injury
(C4-C5)
4 months after irradiation2 × 1054 mm cranial and caudal to the irradiated siteTransplanted mESCs-derived OPCs survive, migrate, and differentiate into oligodendrocytes within the irradiated lesion
Histological examination shows a narrowed cavitation and a dorsal funiculus with increased densities
Locomotion of fore limbs is improved in transplantation group

Keirstead et al. [40]hESCs-derived OPCsContusion spinal cord injury
(T10)
7 days and 10 months after injury1.5 × 1064 mm cranial and caudal to the lesion center7-day group: OPCs survive, differentiate into oligodendrocytes, and remyelinate axons; BBB scores are significantly higher in OPCs-treated rats
10-day group: OPCs survive and differentiate into oligodendrocytes but do not participate in remyelination; there is no improvement in BBB scores

Sharp et al. [41]hESCs-derived OPCsContusion spinal cord injury
(C5)
7 days after injury1.5 × 106Cranial and caudal to the lesion center (interval is unknown)Transplanted cells survive, redistribute, and differentiate in the injury sites; OPCs-remyelination efficiency is much higher
BBB scores, forelimb stride length, and range of motion are improved significantly
OPCs transplantation improves axon sparing and attenuates cavitation; it also alters the injury-induced gene expression (IL10, Fas, HGF, etc.)

All et al. [42]hESCs-derived OPCsContusion spinal cord injury (T8)2 hours after injury1 × 106Lesion site;
4 mm cranial and 1 mm left;
4 mm caudal and 1 mm right
Transplanted cells survive and differentiate into myelinating oligodendrocytes while no astrogenesis is observed
OPCs transplantation shows improvement in SSEPs amplitudes and latencies
Cavitation in treated group is attenuated, and LFB staining is much higher

Kerr et al. [43]hESCs-derived OPCsContusion spinal cord injury (T8)3 and 24 hours after injury1.5 × 105
5 × 105, 
respectively
T7 and T9
And T8
Transplanted cells survive and migrate well without tumor or cyst formation
Behavioral and electrophysiological examination improves in the OPCs-treated group

Czepiel et al. [44]iPSCs-derived OPCsIn vitro: coculture of iPSCs-derived OPCs and DRGs
In vivo: cuprizone-induced demyelination mouse model
1 × 105Corpus callosumIn vitro: extensive myelin formation around naked axons
In vivo: 80% cells do not survive the injection, while survived ones develop into mature oligodendrocytes
Teratoma is seen in rats treated with cells containing undifferentiated iPSCs

Pouya et al. [45]iPSCs-derived OPCsOptic chiasm demyelination by lysolecithin1 week after lysolecithin administration2 × 105ChiasmA reduction in latencies of VEPs in transplantation group is seen
Transplanted OPCs integrate and differentiate into oligodendrocytes

All et al. [46]iPSCs-derived OPCsContusion spinal cord injury
(T8)
24 hours after injury5 × 105Lesion siteOPCs transplantation reduces cavitation, scars formation, and microglial proliferation
Transplanted OPCs differentiate and are remyelinated in the lesion
BBB scores improvement is only significantly seen after the first month

Douvaras et al. [47]OPCs induced from iPSCs derived from MS patients (hiPSCs-derived OPCs);
hESCs-derived OPCs
Shiverer/rag2 mice1 × 105 (5 × 104 each side)Bilaterally at a depth of 1.1 mm into the corpus callosumOPCs can be efficiently generated from hiPSCs
Very few hiPSCs-OPCs differentiate into astrocytes, and no neurons are found
Transplanted hiPSCs-OPCs are myelinated in the brain

Czepeil et al. [48]iPSCs-derived OPCs with overexpression of STXIn vitro: coculture of iPSCs-derived OPCs and DRGs
In vivo: cuprizone-induced demyelination mouse model
1 × 105Corpus callosumSTX-treated OPCs show a significantly increased migratory ability in vitro and in vivo
Survival and maturation pattern of STX-treated and control OPCs are similar

BBB scores: Basso, Beattie, and Bresnahan scores; CNTF: ciliary neurotrophic factor; DRGs: dorsal root ganglion neurons; HGF: hepatocyte growth factor; IL-10: interleukin-10; LFB: Luxol fast blue; MBP: myelin basic protein; MEPs: motor evoked potentials; SHH: sonic hedgehog; STX: sialyltransferase X; SSEPs: somatosensory evoke potentials; tcMMEPs: transcranial magnetic motor-evoked potential; VEPs: visual evoked potentials.