Transplantation of human umbilical cord mesenchymal stem cells to repair myelination disorders in neonatal rats with white matter injury

Zhang Shujuan; Xu Qianqian; Wang Chao; Li Yunhui; Zhu Yanping

doi:10.12307/2026.248

Abstract：BACKGROUND:Myelination deficits are a core feature of white matter injury in preterm infants.In recent years,human umbilical cord mesenchymal stem cells have been applied in various animal models of brain injury,demonstrating the capacity to promote myelin repair.Elucidating the regulatory mechanisms by which human umbilical cord mesenchymal stem cells enhance neural myelination will contribute to optimizing therapeutic strategies and facilitating clinical translation. OBJECTIVE:To clarify the reparative effect of human umbilical cord mesenchymal stem cells on myelination disorders caused by maturation arrest of the oligodendrocyte lineage in neonatal rats with white matter injury. METHODS:Seventy-two two-day-old Sprague-Dawley rats were randomly divided into a sham-operated group,a white matter injury group,and a human umbilical cord mesenchymal stem cell transplantation group,with twenty-four rats in each group.A neonatal rat white matter injury model was established by a combination of low-dose lipopolysaccharide and hypoxia-ischemia.Fourteen days after modeling,hematoxylin-eosin staining was used to observe pathological changes in white matter.Immunohistochemistry,western blotting,and real-time quantitative polymerase chain reaction were used to detect the positive expression,protein expression,and mRNA expression levels of oligodendrocyte transcription factor 2,glial antigen 2,and myelin basic protein.Twenty-eight days after modeling,Luxol fast blue staining was performed to observe myelin formation,and the Morris water maze test was used to evaluate spatial learning and memory ability. RESULTS AND CONCLUSION:(1)Fourteen days after modeling,hematoxylin-eosin staining showed that a large number of cells in the white matter injury group were degenerated and necrotic,and the arrangement of nerve fibers was disordered;while the cell morphology in the human umbilical cord mesenchymal stem cell transplantation group was close to normal,and the nerve fibers were arranged more neatly.(2)On day 14 after modeling,there was no statistically significant difference in the positive expression,protein,and mRNA levels of oligodendrocyte transcription factor 2 among the groups(P>0.05).Compared with the sham-operated group,the positive expression,protein,and mRNA levels of glial antigen 2 in the white matter injury group were upregulated(P<0.05),while the positive expression,protein,and mRNA levels of myelin basic protein were downregulated(P<0.05).Compared with the white matter injury group,the positive expression,protein,and mRNA levels of glial antigen 2 in the human umbilical cord mesenchymal stem cell transplantation group were downregulated(P<0.05),while the positive expression,protein,and mRNA levels of myelin basic protein were upregulated(P<0.05).(3)On day 28 after modeling,Luxol fast blue staining results showed that compared with the sham-operated group,the white matter injury group had decreased myelin expression(P<0.05).Compared with the white matter injury group,the human umbilical cord mesenchymal stem cell transplantation group had increased myelin expression(P<0.05).(4)On day 28 after modeling,Morris water maze results showed that compared with the sham-operated group,the white matter injury group had prolonged escape latency and decreased platform crossing times(P<0.05).Compared with the white matter injury group,the human umbilical cord mesenchymal stem cell transplantation group had shortened escape latency and increased platform crossing times(P<0.05).There was no statistical difference in average swimming distance between the groups(P>0.05).These results suggest that human umbilical cord mesenchymal stem cells can promote the maturation of oligodendrocytes in neonatal rats with white matter injury,repair myelination disorders,and improve cognitive function.