Laboratory of Stem Cells and Cell Reprogramming, Department of Biomedical Engineering (BK21 plus program), Dongguk University, Seoul 100-715, Republic of Korea.
Laboratory of Protein Engineering, Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Republic of Korea.
Nat Nanotechnol. 2017 Oct;12(10):1006-1014. doi: 10.1038/nnano.2017.133. Epub 2017 Jul 17.
Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes. In vivo dopaminergic neuron reprogramming by EMF stimulation of AuNPs efficiently and non-invasively alleviated symptoms in mouse Parkinson's disease models. This study provides a proof of principle for EMF-based in vivo lineage conversion as a potentially viable and safe therapeutic strategy for the treatment of neurodegenerative disorders.
电磁场(EMF)是由带电物体产生的物理能量场,特定范围的 EMF 可以影响许多生物过程,包括细胞命运和可塑性的控制。在这项研究中,我们表明,在特定的 EMF 条件下,被电磁化的金纳米粒子(AuNPs)有助于在体外和体内有效地将诱导多巴胺神经元进行直接谱系重编程。值得注意的是,电磁刺激导致组蛋白乙酰转移酶 Brd2 的特异性激活,导致组蛋白 H3K27 乙酰化和神经元特异性基因的强烈激活。通过 AuNPs 的 EMF 刺激对体内多巴胺能神经元的重编程有效地、非侵入性地缓解了小鼠帕金森病模型中的症状。这项研究为基于 EMF 的体内谱系转换提供了原理证明,作为治疗神经退行性疾病的一种潜在可行和安全的治疗策略。