中国病理生理杂志2025,Vol.41Issue(5):843-850,8.DOI:10.3969/j.issn.1000-4718.2025.05.002
人少突胶质前体细胞移植对血管性痴呆小鼠脑白质的影响
Effects of human oligodendrocyte precursor cell transplantation on cere-bral white matter in mice with vascular dementia
摘要
Abstract
AIM:We investigated the survival,migration and differentiation abilities of human oligodendro-cyte precursor cells(hOPC)in the brains of mice with vascular dementia(VaD),the effects of hOPC on cerebral white matter,and the underlying mechanisms.METHODS:Mouse VaD model was constructed using the bilateral common ca-rotid artery stenosis method,and the mice were randomly divided into sham,VaD and hOPC groups.Eight weeks after model establishment,the mice in VaD and hOPC groups received equal volume of vehicle(PBS)and hOPC solution,re-spectively,through the corpus callosum.Survival,migration and differentiation of hOPC in the brain were observed by im-munofluorescence staining at 4 and 12 weeks after transplantation.Twelve weeks after transplantation,the effects of hOPC on mouse brain white matter were detected by immunofluorescence staining of myelin basic protein(MBP),myelin-associ-ated glycoprotein(MAG),neurofilament protein 200(NF200)and non-phosphorylated neurofilament H(using monoclo-nal antibody SMI32),and by water maze experiments.Paracrine signaling by hOPC was explored using immunofluores-cence staining for vascular endothelial growth factor(VEGF).RESULTS:The hOPC survived in the brains of VaD mice for 12 weeks,migrated to damaged white matter areas,and partially differentiated into mature oligodendrocytes(approxi-mately 64%).Twelve weeks after transplantation,hOPC significantly increased the fluorescence intensity of MBP,MAG,and NF200(P<0.05 or P<0.01)and decreased the fluorescence intensity of SMI32(P<0.01).The VEGF expression in hOPC-treated mice was significantly higher than that in sham and VaD groups(P<0.01).The difference in water maze test performance between hOPC and sham groups was not statistically significant(P>0.05).The mice in hOPC group had a shorter latency than those in VaD group(P<0.05 or P<0.01),and performed more platform crossings than those in VaD group(P<0.05).CONCLUSION:The hOPC can survive,migrate and differentiate in the brains of VaD mice,attenuate cerebral white matter lesions,and improve cognitive function.These improvements may be attributed to cell replacement and paracrine effects.关键词
血管性痴呆/白质/少突胶质前体细胞/干细胞移植/旁分泌Key words
vascular dementia/white matter/oligodendrocyte precursor cells/stem cell transplantation/paracrine分类
临床医学引用本文复制引用
周杰,刘卫鹏,杨辉,汪兆艳,王倩,栾佐,屈素清..人少突胶质前体细胞移植对血管性痴呆小鼠脑白质的影响[J].中国病理生理杂志,2025,41(5):843-850,8.基金项目
国家重点研发计划项目(No.2017YFA0104200) (No.2017YFA0104200)