title: Selective neuronal differentiation of neural stem cells induced by nanosecond microplasma agitation.
abstract: An essential step for therapeutic and research applications of stem cells is their ability to differentiate into specific cell types. Neuronal cells are of great interest for medical treatment of neurodegenerative diseases and traumatic injuries of central nervous system (CNS), but efforts to produce these cells have been met with only modest success. In an attempt of finding new approaches, atmospheric-pressure room-temperature microplasma jets (MPJs) are shown to effectively direct in vitro differentiation of neural stem cells (NSCs) predominantly into neuronal lineage. Murine neural stem cells (C17.2-NSCs) treated with MPJs exhibit rapid proliferation and differentiation with longer neurites and cell bodies eventually forming neuronal networks. MPJs regulate ~75% of NSCs to differentiate into neurons, which is a higher efficiency compared to common protein- and growth factors-based differentiation. NSCs exposure to quantized and transient (~150 ns) micro-plasma bullets up-regulates expression of different cell lineage markers as β-Tubulin III (for neurons) and O4 (for oligodendrocytes), while the expression of GFAP (for astrocytes) remains unchanged, as evidenced by quantitative PCR, immunofluorescence microscopy and Western Blot assay. It is shown that the plasma-increased nitric oxide (NO) production is a factor in the fate choice and differentiation of NSCs followed by axonal growth. The differentiated NSC cells matured and produced mostly cholinergic and motor neuronal progeny. It is also demonstrated that exposure of primary rat NSCs to the microplasma leads to quite similar differentiation effects. This suggests that the observed effect may potentially be generic and applicable to other types of neural progenitor cells. The application of this new in vitro strategy to selectively differentiate NSCs into neurons represents a step towards reproducible and efficient production of the desired NSC derivatives.
authors.affiliation: State Key Laboratory of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Chinese National Center of Plant Gene Research (Wuhan) HUST Part, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan 430074, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.affiliation: The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Chinese National Center of Plant Gene Research (Wuhan) HUST Part, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan 430074, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China. Electronic address: luxinpei@hotmail.com.
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.affiliation: The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Chinese National Center of Plant Gene Research (Wuhan) HUST Part, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan 430074, PR China. Electronic address: hegy@hust.edu.cn.
authors.forename: G
authors.initials: G
authors.lastname: He
authors.affiliation: The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Chinese National Center of Plant Gene Research (Wuhan) HUST Part, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan 430074, PR China.
authors.forename: G
authors.initials: G
authors.lastname: Yang
authors.affiliation: The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Chinese National Center of Plant Gene Research (Wuhan) HUST Part, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan 430074, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.affiliation: Transformational Biology TCP and Plasma Nanoscience Laboratories, CSIRO Materials Science and Engineering, P. O. Box 218, Lindfield, NSW 2070, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Ishaq
authors.affiliation: Transformational Biology TCP and Plasma Nanoscience Laboratories, CSIRO Materials Science and Engineering, P. O. Box 218, Lindfield, NSW 2070, Australia; Brain Dynamics Group, Complex Systems, School of Physics, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: kostya.ostrikov@csiro.au.
authors.forename: K
authors.initials: K
authors.lastname: Ostrikov
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D051379:Mice; D008846:Micromanipulation / Q000379:methods*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D058626:Plasma Gases; D051381:Rats
chemical_list: D058626:Plasma Gases