Exogenous Oligodendrocyte Progenitor Cell Transplantation Results in Structural and Functional Recovery in a Preterm Infant Cerebral White Matter Injury Rat Model

Background: Cerebral white matter injury (WMI) is the most common brain injury in preterm infants; it leads to motor and developmental deficits and is often accompanied by cognitive impairment. WMI is characterized by the loss of pre-myelinating oligodendrocytes. Regeneration therapies for preterm neonates with WMI are still in the preclinical phase, among which oligodendrocyte progenitor cell (OPC) transplantation is a promising approach. One promising approach for treating preterm infants is cell replacement therapy, in which lost cells are replaced by human OPCs (hOPCs) derived from human neural stem cells (hNSCs). MethodsIn this study, we developed a method to induce the differentiation of hNSCs into hOPCs. OLIG2 + /NG2 + /PDGFRα + /O4 + hOPCs were enriched and transplanted into the corpus callosum of a preterm infant WMI rat model. ResultsTransplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histology and Magnetic resonance imaging (MRI) revealed lesioned structural repair. Electron microscopy revealed the re-myelination of the axons in the corpus callosum. The Morris water maze test revealed a recovery of cognitive function. ConclusionsOur study showed that transplantation of hOPCs derived from hNSCs is a viable therapeutic strategy for cerebral WMI. The results of our study contribute to the further development of cell therapeutic strategies.