Yeo Hancheol, Kim Yoo Jung, Seok Jaekwon, Kwak Yeonjoo, Jang Soo Bin, Lim Na Hee, Song Kwonwoo, Lee Junghoon, Cho Min Chul, Kim Soo Woong, Cho Ssang-Goo
Department of Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Molecular & Cellular Reprogramming Center, Institute of Advanced Regenerative Science, and Institute of Health, Aging & Society, Konkuk University, Seoul, 05029, Republic of Korea.
R&D Team, StemExOne Co., Ltd., Gwangjin-gu, Seoul, 05029, Republic of Korea.
Acta Neuropathol Commun. 2025 May 27;13(1):118. doi: 10.1186/s40478-025-02033-9.
Neurological damage caused by peripheral nerve injury can be devastating and is a common neurological disorder that, along with muscle disorders, reduces the quality of life. Neural crest cells (NCCs) are a transient cell population that occurs during embryogenesis, can differentiate into various cells upon transplantation, and has potential therapeutic effects on neurological diseases. However, there are limitations to cell therapy, such as uncontrolled differentiation and tumor formation. Extracellular vesicles (EVs), which are non-cellular potential therapeutic candidates, are nanosized membrane-bound vesicles. Studies have been reported using starch cells derived from neural cells, such as neural stem cells, because they are involved in cell-to-cell communication and carry a variety of bioactive molecules. We investigated the effects of EVs isolated from NCCs on neuronal cell death and inflammation. Additionally, we overexpressed the nerve growth factor (NGF), which is involved in neural cell growth and proliferation, in NCCs to further investigate the effects of EVs containing NGF. NCC-EVs showed neuroprotective and regenerative properties by modulating inflammatory pathway, promoting Schwann cell activation, and enhancing remyelination. In vitro studies on NCC-EVs suppressed pro-inflammatory cytokines and reduced oxidative stress-induced neuronal apoptosis through NF-κB pathway inhibition and ERK, AKT signal activation. We also evaluated the effect of EVs on neuropathy by performing in vivo study. Our results suggest that NCC-EV had neuroprotective effects by reducing neuronal apoptosis and promoting neuronal proliferation based on neurite outgrowth and anti-inflammation effects treated with NCC-EVs. In addition, NCC-EVs were protected muscle loss caused by peripheral nerve injury. NCC-EV induced regeneration of damaged nerves and inhibited cell death through anti-inflammatory effects. This study suggests the potential of NGF-enriched EVs as non-cellular therapeutic platform for peripheral neuropathies and other neuroinflammatory disorders.
周围神经损伤引起的神经损伤可能是毁灭性的,并且是一种常见的神经疾病,它与肌肉疾病一起会降低生活质量。神经嵴细胞(NCCs)是胚胎发育过程中出现的一种短暂细胞群体,移植后可分化为各种细胞,对神经疾病具有潜在治疗作用。然而,细胞治疗存在局限性,如分化不受控制和肿瘤形成。细胞外囊泡(EVs)是无细胞的潜在治疗候选物,是纳米级的膜结合囊泡。已有研究报道使用源自神经细胞(如神经干细胞)的淀粉样细胞,因为它们参与细胞间通讯并携带多种生物活性分子。我们研究了从NCCs中分离的EVs对神经元细胞死亡和炎症的影响。此外,我们在NCCs中过表达参与神经细胞生长和增殖的神经生长因子(NGF),以进一步研究含有NGF的EVs的作用。NCC-EVs通过调节炎症途径、促进雪旺细胞活化和增强髓鞘再生,表现出神经保护和再生特性。对NCC-EVs的体外研究通过抑制NF-κB途径和激活ERK、AKT信号,抑制促炎细胞因子并减少氧化应激诱导的神经元凋亡。我们还通过体内研究评估了EVs对神经病变的影响。我们的结果表明,NCC-EV通过减少神经元凋亡、促进基于神经突生长的神经元增殖以及NCC-EVs治疗的抗炎作用,具有神经保护作用。此外,NCC-EVs可保护周围神经损伤引起的肌肉损失。NCC-EV诱导受损神经的再生并通过抗炎作用抑制细胞死亡。这项研究表明,富含NGF的EVs作为周围神经病变和其他神经炎症性疾病的无细胞治疗平台具有潜力。
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