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Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy

Nature Nanotechnology volume 12, pages 1006–1014 (2017)Cite this article

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Abstract

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.

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Figure 1: EMF stimulation magnetizes AuNPs.
Figure 2: Efficient direct lineage reprogramming of somatic fibroblasts into iDA neurons on EMF-induced magnetized AuNPs.
Figure 3: Molecular mechanisms of direct lineage reprogramming by EMF-induced magnetized AuNPs.
Figure 4: Histone acetylation mediates EMF-induced efficient direct lineage reprogramming.
Figure 5: Efficient direct lineage reprogramming of human cells into iDA neurons on EMF-induced magnetized AuNPs.
Figure 6: Rescue of Parkinsonian phenotypes in MPTP- and 6-OHDA-induced PD mouse models by in vivo direct lineage reprogramming using the EMF-induced magnetized AuNP system.

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Acknowledgements

This work was supported by the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (NRF-2017M3A9C6029306, 2016R1A2B2014195, 2013M3A9B4076483, NRF-2015 M3A9B4051064), Korea Health Technology R&D Project, Ministry of Health & Welfare (HI16C1176), the Next-Generation BioGreen 21 Program, Rural Development Administration (PJ011077) and the Ministry of Food and Drug Safety in 2017 (14172MFDS974).

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Authors and Affiliations

  1. Department of Biomedical Engineering (BK21 plus program), Laboratory of Stem Cells and Cell Reprogramming, Dongguk University, Seoul, 100-715, Republic of Korea

    Junsang Yoo, Hongwon Kim, Yujung Chang, Jaein Shin, Soonbong Baek & Jongpil Kim

  2. Department of Biomedical Engineering, Laboratory of Protein Engineering, Dongguk University, Seoul, 100-715, Republic of Korea

    Euiyeon Lee & Youngeun Kwon

  3. Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu, 45158, Republic of Korea

    Hee Young Kim

  4. Department of Oral Physiology, School of Dentistry, Kyungpook National University, 2177, Dalgubeol Boulevard, Jung-gu, 41940, Daegu, Republic of Korea

    Dong-ho Youn, Wonhee Jang & Won Jun

  5. Department of Life Science, Dongguk University, Seoul, 188-26, Republic of Korea

    Junghyun Jung

  6. College of Pharmacy, Kyung Hee University, Seoul, 02447, Korea

    Wonwoong Lee & Jongki Hong

  7. Department of Electrical and Electronic Engineering, Hankyong National University, Kyonggi-do, 456-749, Republic of Korea

    Soochan Kim

  8. Studies of Translational Acupuncture Research (STAR), Acupuncture & Meridian Science Research Center (AMSRC), Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 130-701, Republic of Korea

    Hi-Joon Park

  9. Department of Biomedical Sciences, School of Veterinary Medicine and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Christopher J. Lengner

  10. BIO-FD&C Co. 509-511, Smart Valley A, 30, Songdomirai-ro, 21990, Incheon, Republic of Korea

    Sang Hyun Moh

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Contributions

J.Y., Y.K. and J.K. designed the study. J.Y., E.L., H.Y.K., D.Y., J.J., H.K., Y.C., W.L., J.S., S.B., W.Jang, W.Jun, S.K., J.H. and H.P. performed the experiments. J.Y., J.K. and C.J.L. analysed the data. Y.K., E.L., H.Y.K., D.Y. and S.H.M. contributed materials and/or analysis tools. The manuscript was written based on contributions by all the authors. All the authors approved the final version of the manuscript.

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Correspondence to Jongpil Kim.

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Yoo, J., Lee, E., Kim, H. et al. Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy. Nature Nanotech 12, 1006–1014 (2017). https://doi.org/10.1038/nnano.2017.133

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