Transplanted oligodendrocyte progenitor cells improve neurological defects in a rat model of preterm white-matter injury during the sequela phase.

Abstract

Background: Preterm white-matter injury (PWMI), frequently occurring in preterm infants, is a major factor contributing to long-term neurological impairment and is a prevalent form of brain injury in this population. Therapies for this condition mainly target the acute phase, often leaving the chronic sequelae phase untreated. This study aimed to examine how transplanted human oligodendrocyte progenitor cells (hOPCs) differentiate and their therapeutic effectiveness in a rat model of PWMI sequelae.

Methods: Hypoxia-ischemia was induced in neonatal rats at 3 days after birth and was followed by intracerebral transplantation of hOPCs (5×10⁵ cells in 4 µL) 3 weeks later. Neurobehavioral assessment was performed using the Morris water maze test 9-10 weeks after transplantation. After cardiac perfusion, pathological staining, immunohistochemical (IHC) analysis, and transmission electron microscopy (TEM) were conducted.

Results: Transplanted hOPCs remained viable in the brains of rats with PWMI sequelae for up to 13 weeks. They were found to be extensively dispersed in the damaged white matter and traversed along the corpus callosum toward the opposite hemisphere. About 83.34%±3.81% of the transplanted cells underwent differentiation to become oligodendrocyte lineage cells, among which about 77.15%±3.06% matured into oligodendrocytes that myelinated axons. IHC staining and TEM analyses showed that the myelin basic protein fluorescence intensity and myelin thickness were increased, pathological staining indicated that white-matter fiber injury was ameliorated, and the results of the Morris water maze test suggested that the cognitive function and neurobehavioral performance of the rats receiving transplanted hOPCs were restored.

Conclusions: Transplanted hOPCs promoted remyelination, reduced white-matter injury, and improved neurobehavioral outcomes in PWMI rats during the sequela phase, suggesting that transplantation of hOPCs may be an effective therapeutic approach for children with neurological deficits associated with PWMI.