Wang Zhaoyan, Zhang Leping, Yang Yinxiang, Wang Qian, Qu Suqing, Wang Xiaohua, He Zhixu, Luan Zuo
Laboratory of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, People's Republic of China.
Guizhou Medical University, Guiyang, 550004, People's Republic of China.
Neuropsychiatr Dis Treat. 2023 Sep 11;19:1935-1947. doi: 10.2147/NDT.S414493. eCollection 2023.
Cerebral white matter injury (WMI) is the most common brain injury in preterm infants, leading to motor and developmental deficits often accompanied by cognitive impairment. However, there is no effective treatment. One promising approach for treating preterm WMI is cell replacement therapy, in which lost cells can be replaced by exogenous oligodendrocyte progenitor cells (OPCs).
This study developed a method to differentiate human neural stem cells (hNSCs) into human OPCs (hOPCs). The preterm WMI animal model was established in rats on postnatal day 3, and OLIG2/NG2/PDGFRα/O4 hOPCs were enriched and transplanted into the corpus callosum on postnatal day 10. Then, histological analysis and electron microscopy were used to detect lesion structure; behavioral assays were performed to detect cognitive function.
Transplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histological analysis revealed structural repair of lesioned areas. Re-myelination of the axons in the corpus callosum was confirmed by electron microscopy. The Morris water maze test revealed cognitive function recovery.
Our study showed that exogenous hOPCs could differentiate into CC1 OLS in the brain of WMI rats, improving their cognitive functions.
脑白质损伤(WMI)是早产儿最常见的脑损伤,会导致运动和发育缺陷,常伴有认知障碍。然而,目前尚无有效的治疗方法。治疗早产WMI的一种有前景的方法是细胞替代疗法,即通过外源性少突胶质前体细胞(OPCs)替代受损细胞。
本研究开发了一种将人神经干细胞(hNSCs)分化为人OPCs(hOPCs)的方法。在出生后第3天建立早产WMI大鼠动物模型,并在出生后第10天富集OLIG2/NG2/PDGFRα/O4 hOPCs并将其移植到胼胝体中。然后,采用组织学分析和电子显微镜检测损伤结构;进行行为学检测以检测认知功能。
移植的hOPCs存活并迁移至整个主要白质束。观察到移植的hOPCs发生形态学分化。组织学分析显示损伤区域结构修复。电子显微镜证实胼胝体轴突重新髓鞘化。莫里斯水迷宫试验显示认知功能恢复。
我们的研究表明,外源性hOPCs可在WMI大鼠脑内分化为CC1 OLS,改善其认知功能。