差异化状态和培养条件影响神经干细胞/原始细胞衍生的细胞外囊泡生物活性
Dipankar Dutta1, Nicholas H Pirolli1, Daniel Levy1
1Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA. smjay@umd.edu.
Biomaterials science
|June 27, 2023
概括
神经原生干细胞外细胞囊泡 (EVs) 显示治疗潜力,但需要优化条件. 用神经生长因子 (NGF) 标准化NPSC EV生产可增强神经再生,改善临床前模型的结果.
科学领域:
- 神经科学是一个神经科学.
- 再生医学是一种再生医学.
- 细胞生物学 细胞生物学
背景情况:
- 来自神经原生/干细胞 (NPSC) 的细胞外囊 (EV) 显示出神经再生的临床前前景.
- 由于非标准化培养条件,NPSC具有局限性,包括缺乏髓化能力和不一致的EV产量.
- 寡类细胞前体细胞 (OPCs) 和不成熟的寡类细胞 (iOLs) 更有差异化,可能产生更优异的EVs.
研究的目的:
- 为了比较由OPCs和iOLs衍生的EVs与NPSCs的神经治疗潜力.
- 研究细胞外基质 (ECM) 涂层和生长因子对EV特性的影响.
- 优化NPSC电动汽车生产以提高神经再生能力.
主要方法:
- 在各种培养条件下 (ECM涂层,NGF等生长因子) 从NPSCs,OPCs和iOLs生成EV.
- 评估了EVs在细胞增殖,抗炎性测试和神经元外生中的生物活性.
- 使用*in vivo*大鼠神经压伤模型来评估优化NPSC EVs对轴突再生和再内核化的有效性.
主要成果:
- 在扩散和抗炎性测试中,OPC和iOL EVs的表现与NPSC EVs相提并论.
- 在神经元外生长试验中,NPSC EVs表现出卓越的性能.
- 神经生长因子 (NGF) 显著增强了NPSC EV生物活性.
- 优化的NPSC EVs (纤维肌菌素 + NGF) 在大鼠神经压伤损伤模型中显著改善了轴突再生和肌肉再生.
结论:
- 虽然OPC和iOL电动汽车具有潜力,但NPSC电动汽车在最佳条件下生产时,表现出显著的神经再生能力.
- 培养条件的标准化,特别是NGF的纳入,对于最大限度地提高NPSC衍生的EVs的治疗效果至关重要.
- 优化的NPSC EVs代表了神经损伤的有希望的无细胞疗法.
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