Institute for Regenerative Medicine, Department of Cell Biology and Genetics, Texas A&M University School of Medicine, College Station, TX, USA.
Stem Cells Transl Med. 2023 Mar 17;12(3):140-153. doi: 10.1093/stcltm/szad004.
Extracellular vesicles (EVs) derived from neural stem cells (NSC-EVs), astrocytes (ADEVs), and microglia (MDEVs) have neuroregenerative properties. This review discusses the therapeutic efficacy of NSC-EVs, ADEVs, and MDEVs in traumatic brain injury (TBI) models. The translational value and future directions for such EV therapy are also deliberated. Studies have demonstrated that NSC-EV or ADEV therapy can mediate neuroprotective effects and improve motor and cognitive function after TBI. Furthermore, NSC-EVs or ADEVs generated after priming parental cells with growth factors or brain-injury extracts can mediate improved therapeutic benefits. However, the therapeutic effects of naïve MDEVs are yet to be tested rigorously in TBI models. Studies using activated MDEVs have reported both adverse and beneficial effects. NSC-EV, ADEV, or MDEV therapy for TBI is not ready for clinical translation. Rigorous testing of their efficacy for preventing chronic neuroinflammatory cascades and enduring motor and cognitive impairments after treatment in the acute phase of TBI, an exhaustive evaluation of their miRNA or protein cargo, and the effects of delayed EV administration post-TBI for reversing chronic neuroinflammation and enduring brain impairments, are needed. Moreover, the most beneficial route of administration for targeting EVs into different neural cells in the brain after TBI and the efficacy of well-characterized EVs from NSCs, astrocytes, or microglia derived from human pluripotent stem cells need to be evaluated. EV isolation methods for generating clinical-grade EVs must also be developed. Overall, NSC-EVs and ADEVs promise to mitigate TBI-induced brain dysfunction, but additional preclinical studies are needed before their clinical translation.
外泌体(EVs)来源于神经干细胞(NSC-EVs)、星形胶质细胞(ADVEs)和小胶质细胞(MDVEs),具有神经再生特性。本综述讨论了 NSC-EVs、ADVEs 和 MDVEs 在创伤性脑损伤(TBI)模型中的治疗效果。还审议了这种 EV 治疗的转化价值和未来方向。研究表明,NSC-EV 或 ADVE 治疗可以介导神经保护作用,并改善 TBI 后的运动和认知功能。此外,用生长因子或脑损伤提取物对亲代细胞进行预处理后产生的 NSC-EV 或 ADVE 可以介导改善的治疗益处。然而,幼稚的 MDVEs 在 TBI 模型中的治疗效果尚未经过严格测试。使用激活的 MDVEs 的研究报告了不良反应和有益作用。用于 TBI 的 NSC-EV、ADEV 或 MDV 治疗尚未准备好进行临床转化。需要严格测试它们在 TBI 急性期治疗后预防慢性神经炎症级联反应和持久运动和认知障碍的功效,对其 miRNA 或蛋白质货物进行详尽评估,以及在 TBI 后延迟 EV 给药以逆转慢性神经炎症和持久脑损伤的效果。此外,需要评估在 TBI 后将 EV 靶向大脑中不同神经细胞的最佳给药途径,以及源自人类多能干细胞的 NSCs、星形胶质细胞或小胶质细胞的经过良好表征的 EV 的功效。还必须开发用于生成临床级 EV 的 EV 分离方法。总体而言,NSC-EVs 和 ADVEs 有望减轻 TBI 引起的大脑功能障碍,但在进行临床转化之前,还需要进行更多的临床前研究。
Int J Biol Sci. 2025-6-5
Invest Ophthalmol Vis Sci. 2025-4-1
Curr Alzheimer Res. 2024
World J Stem Cells. 2024-12-26
Medicina (Kaunas). 2024-8-24
Intensive Care Med. 2022-6
Front Aging Neurosci. 2022-3-25
Biol Psychiatry. 2022-3-1
Biochem Soc Trans. 2021-8-27
Biol Psychiatry. 2022-3-1