Al-Ward Hisham, Chen Wei, Gao Wenxia, Zhang Chunxue, Yang Xueyan, Xiong Yao, Wang Xinyi, Agila Rafeq, Xu Hui, Sun Yi Eve
Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Stem Cell Rev Rep. 2025 Jan;21(1):236-253. doi: 10.1007/s12015-024-10803-6. Epub 2024 Nov 6.
Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition resulting from impaired oxygen and blood flow to the brain during birth, leading to neuroinflammation, neuronal apoptosis, and long-term neurological deficits. Despite the use of therapeutic hypothermia, current treatments remain inadequate in fully preventing brain damage. Recent advances in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a novel, cell-free therapeutic approach, as these EVs can cross the blood-brain barrier (BBB) and deliver functional microRNAs (miRNAs) to modulate key pathways involved in inflammation and neuroprotection. This review examines how specific miRNAs encapsulated in MSC-EVs-including miR-21, miR-124, miR-146, and the miR-17-92 cluster-target the complex inflammatory responses that drive HIE pathology. By modulating pathways such as NF-κB, STAT3, and PI3K/Akt, these miRNAs influence neuroinflammatory processes, reduce neuronal apoptosis, and promote tissue repair. The aim is to assess the therapeutic potential of miRNA-loaded MSC-EVs in mitigating inflammation and neuronal damage, thus addressing the limitations of current therapies like therapeutic hypothermia.
新生儿缺氧缺血性脑病（HIE）是一种严重病症，由出生时大脑的氧和血流受损所致，会引发神经炎症、神经元凋亡以及长期神经功能缺损。尽管采用了治疗性低温疗法，但目前的治疗在完全预防脑损伤方面仍显不足。间充质干细胞衍生的细胞外囊泡（MSC-EVs）的最新进展提供了一种新型的无细胞治疗方法，因为这些细胞外囊泡能够穿过血脑屏障（BBB）并递送功能性微小RNA（miRNA），以调节参与炎症和神经保护的关键途径。本综述探讨了包裹在MSC-EVs中的特定miRNA——包括miR-21、miR-124、miR-146和miR-17-92簇——如何靶向驱动HIE病理的复杂炎症反应。通过调节诸如NF-κB、STAT3和PI3K/Akt等途径，这些miRNA影响神经炎症过程，减少神经元凋亡，并促进组织修复。目的是评估负载miRNA的MSC-EVs在减轻炎症和神经元损伤方面的治疗潜力，从而解决当前治疗方法（如治疗性低温疗法）的局限性。
