Intranasal delivery of human oligodendrocyte precursor cells enhances regenerative effects in premature rat brain following hypoxic–ischemic injury
Abstract Background White matter injury is a common ischemic brain injury in premature infants and for which there is no effective treatment. Stem cell transplantation has emerged as a novel approach for replacing damaged brain tissues and promoting regenerative processes. Since intracerebral transplantation is not clinically feasible for premature infants, intranasal delivery of cells to the brain is a promising, noninvasive therapeutic approach for restoring the damaged brain. This study was conducted to investigate whether transplanted human oligodendrocyte progenitor cells exhibit neuroprotective effects in a rat model of WMI in premature infants. Methods SD rats aged 3 days were randomly divided into sham group, preterm white matter injury group and nasal transplantation group. Hypoxia–ischemia was induced in 3-day-old rat pups by right carotid artery ligation, followed by exposure to 6% oxygen for 90 min. Rats were intranasally administered the cell suspension (250,000 cells in 6 µL) twice in each nostril (1 × 106 cells total), and myelin basic protein immunofluorescence staining and transmission electron microscopy were performed to assess endogenous myelin growth in the right hemispheres. Behavioral tests, including the Morris water maze, adhesive-removal test, and cylinder rearing test, as well as a gait test, were performed to evaluate the therapeutic effects at 12 weeks after transplantation. Results The cells transplanted from the nose can enter brain tissue of rats 3 days after transplantation. The myelin sheath structure was more compact and the myelin sheath thickness was increased. The nerve function defect was improved 12 weeks after transplantation. Conclusions The intranasal administration of human oligodendrocyte progenitor cells had beneficial therapeutic effects on rehabilitation of the rat hypoxia-ischemia model. This technique is a potential strategy for applying oligodendrocyte progenitor cells in transplantation therapy against white matter injury.
