Chiu Yu-Sung, Wu Kuo-Jen, Yu Seong-Jin, Wu Kun-Lieh, Hsieh Chang-Yi, Chou Yu-Sheng, Chen Kuan-Yu, Wang Yu-Syuan, Bae Eun-Kyung, Hung Tsai-Wei, Lin Shih-Hsun, Lin Chih-Hsueh, Hsu Shu-Ching, Wang Yun, Chen Yun-Hsiang
YJ Biotechnology Co., Ltd., New Taipei City, Taiwan.
School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
Cell Transplant. 2024 Jan-Dec;33:9636897241296366. doi: 10.1177/09636897241296366.
Cerebral ischemic stroke is a major cerebrovascular disease and the leading cause of adult disability. We and others previously demonstrated that transplantation of human Wharton's jelly mesenchymal stromal cells (WJ-MSCs) attenuated neuronal damage and promoted functional improvement in stroke animals. This study aimed to investigate the protective effects of human WJ-MSC exosome (Exo) transplant in cellular and rat models of cerebral stroke. Administration of Exo significantly antagonized glutamate-mediated neuronal loss and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-X nick end labeling (TUNEL) in rat primary cortical neuronal cultures. Adult male rats underwent a 60-min middle cerebral artery occlusion (MCAo); Exo or vehicle was injected through the tail vein 5-10 min after the MCAo. Two days later, the rats underwent a series of behavioral tests. Stroke rats receiving Exo developed a significant improvement in locomotor function and forelimb strength while reductions in body asymmetry and Bederson's neurological score. After the behavioral test, brain tissues were harvested for histological and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses. Animals receiving Exo had less infarction volume, measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Transplantation of Exo increased the expression of protective neurotrophic factors (BMP7, GDNF) and anti-apoptotic factors (Bcl2, Bcl-xL) in the ischemic brain. These findings suggest that early post-treatment with WJ-MSC Exo, given non-invasively through the vein, improved functional recovery and reduced brain damage in the stroke brain.
脑缺血性中风是一种主要的脑血管疾病，也是成年人残疾的主要原因。我们和其他人之前证明，人脐带来源间充质基质细胞（WJ-MSCs）移植可减轻中风动物的神经元损伤并促进功能改善。本研究旨在探讨人WJ-MSC外泌体（Exo）移植在脑卒细胞模型和大鼠模型中的保护作用。在大鼠原代皮质神经元培养物中，Exo给药显著拮抗了谷氨酸介导的神经元损失以及末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）。成年雄性大鼠接受60分钟的大脑中动脉闭塞（MCAo）；MCAo后5-10分钟通过尾静脉注射Exo或赋形剂。两天后，对大鼠进行一系列行为测试。接受Exo的中风大鼠在运动功能和前肢力量方面有显著改善，同时身体不对称性和贝德森神经学评分降低。行为测试后，采集脑组织进行组织学和定量实时逆转录聚合酶链反应（qRT-PCR）分析。通过2,3,5-三苯基氯化四氮唑（TTC）染色测量，接受Exo的动物梗死体积较小。Exo移植增加了缺血脑中保护性神经营养因子（BMP7、GDNF）和抗凋亡因子（Bcl2、Bcl-xL）的表达。这些发现表明，通过静脉非侵入性给予WJ-MSC Exo进行早期治疗，可改善中风大脑的功能恢复并减少脑损伤。
