Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside
1
Department of Neurobiology and Physiology, Xinxiang Medical University, Xinxiang 453003, Henan, China
2
The International-Joint Lab for Non-invasive Neural Modulation/Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University, Xinxiang 453003, Henan, China
3
Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam 13200, Kepala Batas, Penang, Malaysia
4
Department of Biomedical Sciences, Faculty of Medicine, Universiti Putra Malaysia, Seri Kembangan 43400 Selangor, Malaysia
5
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(6), 1489; https://doi.org/10.3390/cells9061489
Received: 10 April 2020 / Revised: 29 May 2020 / Accepted: 12 June 2020 / Published: 18 June 2020
(This article belongs to the Special Issue Induced Pluripotent Stem Cells in Neurodegenerative Diseases: Application for Therapy and Disease Modeling)
Parkinson’s Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Thus, regenerating functional mDA neurons in PD patients may be a cure to the disease. The proof-of-principle clinical trials showed that human fetal graft-derived mDA neurons could restore the release of dopamine neurotransmitters, could reinnervate the striatum, and could alleviate clinical symptoms in PD patients. The invention of human-induced pluripotent stem cells (hiPSCs), autologous source of neural progenitors with less ethical consideration, and risk of graft rejection can now be generated in vitro. This advancement also prompts extensive research to decipher important developmental signaling in differentiation, which is key to successful in vitro production of functional mDA neurons and the enabler of mass manufacturing of the cells required for clinical applications. In this review, we summarize the biology and signaling involved in the development of mDA neurons and the current progress and methodology in driving efficient mDA neuron differentiation from pluripotent stem cells.
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Keywords:
Parkinson’s disease; midbrain dopaminergic neuron; pluripotent stem cells; differentiation; neurodevelopment; small molecules
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MDPI and ACS Style
Wang, M.; Ling, K.-H.; Tan, J.J.; Lu, C.-B. Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside. Cells 2020, 9, 1489. https://doi.org/10.3390/cells9061489
AMA Style
Wang M, Ling K-H, Tan JJ, Lu C-B. Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside. Cells. 2020; 9(6):1489. https://doi.org/10.3390/cells9061489
Chicago/Turabian StyleWang, Mengmeng; Ling, King-Hwa; Tan, Jun J.; Lu, Cheng-Biao. 2020. "Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside" Cells 9, no. 6: 1489. https://doi.org/10.3390/cells9061489
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