Human umbilical cord mesenchymal stem cells alleviate brain injury and promote neuroregeneration via BDNF/TrkB/CREB/PI3K-Akt pathway in preterm rats with intraventricular hemorrhage.
Mingyou Yu, Ziyi Zhang, Xuxian Wu, Baoying Zhang, Yang Hu, Changge Wei, Miao Ran, Manni Cao, Jinhui Zhang, Xueli Ding, Yan Wang, Can Liu, Maoqiong Chen, Jianwei Xu
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Abstract
Objective: To explore the neuroprotective effect and molecular mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) in preterm rats with intraventricular hemorrhage (IVH), and provide experimental basis for clinical treatment of neonatal IVH.
Methods: Tissue block adherence method was used to isolate and culture hUC-MSCs, and P4 Sprague-Dawley premature rats were divided into sham, IVH model, and hUC-MSC treatment groups. Collagenase VIIS was injected to establish IVH model, and hUC-MSCs were injected into lateral ventricles. Cell colonization, body weight, neurobehavior, brain histology, apoptosis, and related molecular indicators were detected via fluorescence tracking, behavioral tests, staining, RT-PCR, Western blot (WB), and ELISA. Bioinformatics combined with ANA12 blocking assay verified core pathways.
Results: hUC-MSCs survived in rat brain for at least 7 days. Compared with the model group, the treatment group gained weight faster, neurobehavioral function was markedly improved, neuronal apoptosis decreased sharply, and brain tissue damage was alleviated. hUC-MSCs up-regulated anti-apoptotic, anti-inflammatory, antioxidant and neurogenesis-related molecules and activated BDNF/TrkB/CREB/PI3K-Akt pathway; TrkB blockade reversed all protective effects.
Conclusion: hUC-MSCs exert multi-target neuroprotection by activating BDNF/TrkB/CREB/PI3K-Akt pathway, which offers a novel strategy for IVH treatment in preterm infants.
目的：探讨人脐带间充质干细胞（hUC-MSCs）对早产大鼠脑室内出血（IVH）的神经保护作用及其分子机制，为新生儿IVH的临床治疗提供实验依据。方法：采用组织块粘附法分离培养hUC-MSC，将P4 Sprague-Dawley早产大鼠分为假手术组、IVH模型组和hUC-MSC治疗组。注射胶原酶VIIS建立IVH模型，侧脑室注射hUC-MSCs。通过荧光跟踪、行为测试、染色、RT-PCR、Western blot （WB）和ELISA检测细胞定植、体重、神经行为、脑组织组织学、凋亡及相关分子指标。生物信息学联合ANA12阻断试验验证了核心通路。结果：hUC-MSCs在大鼠脑内存活至少7天。与模型组比较，给药组大鼠体重增加较快，神经行为功能明显改善，神经元凋亡急剧减少，脑组织损伤减轻。hUC-MSCs上调抗凋亡、抗炎、抗氧化和神经发生相关分子，激活BDNF/TrkB/CREB/PI3K-Akt通路；TrkB阻断逆转了所有的保护作用。结论：hUC-MSCs通过激活BDNF/TrkB/CREB/PI3K-Akt通路发挥多靶点神经保护作用，为早产儿IVH治疗提供了一种新的策略。
期刊介绍：
STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal.
STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes.
The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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