Chen Xingxing, Sai Yipa, Cui Weijing, Hu Xiaoxia, Liu Jing, Cao Xiaofeng, Wu Shili
Department of Pediatrics, Gansu Province People's Hospital, Lanzhou, China.
The First Clinical Hospital, Gansu University of Chinese Medicine, Lanzhou, China.
Adv Clin Exp Med. 2025 Jun;34(6):911-923. doi: 10.17219/acem/192773.
Cerebral palsy (CP) is a neurodevelopmental disorder and motor disorder syndrome. It has been confirmed that mesenchymal stem cells (MSCs) and mouse nerve growth factor (mNGF) can repair brain tissue damage and nerve injury; however, exosomes derived from healthy cells may have a comparable therapeutic potential as the cells themselves.
The purpose of this study was to explore the improvement effect of human umbilical cord mesenchymal stem cell (hUC-MSCs)-derived exosomes on a CP model and determine whether there is a synergistic effect when combined with mNGF.
Exosomes were isolated from hUC-MSCs and examined using transmission electron microscopy (TEM), particle size and western blot (WB). A total of 38 BALB/c mice (male, postnatal day 6 (PND6)) were randomly divided into 5 groups: sham group, CP group, CP-exo group, CP-mNGF group, and CP-exo-mNGF group. Hypoxic induction after unilateral common carotid artery ligation combined with lipopolysaccharide (LPS) infection was used to construct the CP model. Pathological damage to neuron tissue and synaptic structures in the hippocampus was confirmed using light microscopy after hematoxylin-eosin (H&E) staining and TEM, respectively. Survival of neurons was evaluated using Nissl staining. Western blot was applied to monitor PSD-95 and synaptophysin (SYN) protein levels.
This study indicated that exosomes released by hUC-MSCs ameliorated brain damage and synaptic structure destruction in CP mice induced by hypoxic ischemia and LPS infection. When combined with mNGF, there was more effective improvement. In the CP group, neuronal function was severely impaired; however, hUC-MSCs-derived exosomes and mNGF improved it. PSD-95 and SYN proteins were presynaptic and postsynaptic proteins, respectively. Interestingly, the PSD-95 and SYN protein levels were significantly lower in the CP mice, but with the addition of hUC-MSCs-exosomes or mNGF, they increased significantly, especially in the CP-exo-mNGF group.
The nerve function injury in CP can be improved the most when hUC-MSCs-derived exosomes are combined with mNGF through intraperitoneal (ip.) administration.
脑瘫（CP）是一种神经发育障碍和运动障碍综合征。已经证实间充质干细胞（MSCs）和小鼠神经生长因子（mNGF）可以修复脑组织损伤和神经损伤；然而，源自健康细胞的外泌体可能具有与细胞本身相当的治疗潜力。
本研究旨在探讨人脐带间充质干细胞（hUC-MSCs）来源的外泌体对脑瘫模型的改善作用，并确定与mNGF联合使用时是否存在协同效应。
从hUC-MSCs中分离出外泌体，并使用透射电子显微镜（TEM）、粒度分析和蛋白质免疫印迹（WB）进行检测。将38只BALB/c小鼠（雄性，出生后第6天（PND6））随机分为5组：假手术组、脑瘫组、脑瘫-外泌体组、脑瘫-mNGF组和脑瘫-外泌体-mNGF组。采用单侧颈总动脉结扎联合脂多糖（LPS）感染后的缺氧诱导方法构建脑瘫模型。分别使用苏木精-伊红（H&E）染色后的光学显微镜和TEM确认海马体中神经元组织和突触结构的病理损伤。使用尼氏染色评估神经元的存活情况。应用蛋白质免疫印迹法监测突触后致密蛋白95（PSD-95）和突触素（SYN）蛋白水平。
本研究表明，hUC-MSCs释放的外泌体改善了缺氧缺血和LPS感染诱导的脑瘫小鼠的脑损伤和突触结构破坏。与mNGF联合使用时，改善效果更明显。在脑瘫组中，神经元功能严重受损；然而，hUC-MSCs来源的外泌体和mNGF改善了这种情况。PSD-95和SYN蛋白分别是突触前和突触后蛋白。有趣的是，脑瘫小鼠中PSD-�5和SYN蛋白水平显著降低，但添加hUC-MSCs-外泌体或mNGF后，它们显著增加，尤其是在脑瘫-外泌体-mNGF组。
通过腹腔注射将hUC-MSCs来源的外泌体与mNGF联合使用时，对脑瘫神经功能损伤的改善效果最佳。
