Abdelmaboud Salma S, Moss Lauren D, Hudson Charles, Patel Rekha, Avlas Marta, Wohlfahrt Jessica, Wolf Tiara, Guergues Jennifer, Stevens Stanley M, Patel Niketa A, Bickford Paula C
Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
Department of Neurosurgery, Brain and Spine, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
Cells. 2025 Aug 22;14(17):1304. doi: 10.3390/cells14171304.
Traumatic brain injury (TBI) is a major cause of long-term neurological impairment, with aging amplifying vulnerability and worsening recovery. Older individuals face greater cognitive and motor deficits post-TBI and respond less effectively to treatments, as both aging and TBI independently elevate neuroinflammation and cognitive decline. This study evaluated the therapeutic effects of human adipose-derived stem cell small extracellular vesicles (hASC-sEVs) on neurological recovery and neuroinflammation in a mouse model of TBI. Male C57BL/6 mice (3, 15, and 20 months old) underwent controlled cortical impact (CCI) and received intranasal hASC-sEVs 48 h post-injury; control groups received PBS. A dose-response study at 7 days post injury (dpi) identified 20 µg as the optimal therapeutic dose, improving motor function, reducing neuroinflammation, and enhancing neurogenesis. This was followed by a 30-dpi study assessing cognitive function, neuroinflammation, neurogenesis, and proteomic changes in microglia and astrocytes via mass spectrometry. hASC-sEV treatment significantly improved behavioral outcomes and reduced neuroinflammatory markers (GFAP, IBA-1, and MHC-II), with reduced efficacy observed in older mice. Proteomics revealed that hASC-sEVs reduce inflammatory proteins (TNF-α, IL-1β, IFNG, CCL2) and modulated mitochondrial dysfunction and reactive oxygen species. These results highlight hASC-sEVs as a promising cell-free therapy for improving TBI outcomes, especially in aging populations.
创伤性脑损伤（TBI）是长期神经功能障碍的主要原因，随着年龄增长，易感性增加，恢复情况恶化。老年个体在TBI后面临更大的认知和运动缺陷，对治疗的反应也较差，因为衰老和TBI都会独立地加剧神经炎症和认知衰退。本研究评估了人脂肪来源干细胞小细胞外囊泡（hASC-sEVs）对TBI小鼠模型神经恢复和神经炎症的治疗效果。雄性C57BL/6小鼠（3、15和20月龄）接受控制性皮质撞击（CCI），并在受伤后48小时经鼻给予hASC-sEVs；对照组接受PBS。损伤后7天（dpi）的剂量反应研究确定20μg为最佳治疗剂量，可改善运动功能、减轻神经炎症并促进神经发生。随后进行了一项30-dpi的研究，通过质谱分析评估认知功能、神经炎症、神经发生以及小胶质细胞和星形胶质细胞的蛋白质组变化。hASC-sEV治疗显著改善了行为结果并降低了神经炎症标志物（GFAP、IBA-1和MHC-II），在老年小鼠中观察到疗效降低。蛋白质组学显示，hASC-sEVs可减少炎症蛋白（TNF-α、IL-1β、IFNG、CCL2），并调节线粒体功能障碍和活性氧。这些结果突出了hASC-sEVs作为一种有前景的无细胞疗法，可改善TBI的预后，尤其是在老年人群中。
