Functional Differentiation of Neural Stem Cells into Neuronal Subtypes: A Biological Tool for Developmental Neurotoxicity Studies

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Authors

  • Developmental Toxicology Laboratory, System Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), 31, Vishvigyan Bhawan, MG Marg, Lucknow – 226001, Uttar Pradesh ,IN
  • Department of Zoology, Maharishi University of Information Technology Sitapur Road (IIM Bypass, Bhitauli Tiraha), P. O. Maharishi Vidya Mandir, Lucknow – 226013, Uttar Pradesh ,IN
  • Department of Zoology, Maharishi University of Information Technology Sitapur Road (IIM Bypass, Bhitauli Tiraha), P. O. Maharishi Vidya Mandir, Lucknow – 226013, Uttar Pradesh ,IN

DOI:

https://doi.org/10.18311/jeoh/2018/17925

Keywords:

Nerve Growth Factor, Neural Stem Cells, Neuronal Subtypes.
English

Abstract

Neural Stem Cells (NSCs), owing to their potential to get differentiated into various mature cell subtypes including neuronal cells have proved to be an indefinite source of 'raw material' for their application in developmental neurotoxicity as well as therapeutic intervention in neurodegenerative disorders. However, applications of NSCs for such purposes have been broadly limited by lack of enough methods for their directed differentiation. Herein, we describe a chemically defined protocol for efficient differentiation of rat neural stem cells to neuronal subtypes using an 8-day time period. NSCs, subject to NGF (50 ng/mL) were differentiated into neuronal sub-types supplemented with a cocktail of growth factors and supplements. Differentiating cells revealed a gradual and significant induction in the neuronal markers and a parallel decrease in markers of stemness as confirmed by immunocytochemical and translational analysis. The expression of markers was found to be maximum at day 8 of differentiation. Such selective differentiation of NSCs into neurons could offer an imperative step towards generation of NSC derivatives that could facilitate their utilization for research studies.

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Published

2019-01-30

How to Cite

Pandey, A., Singh, M., & Singh, M. (2019). Functional Differentiation of Neural Stem Cells into Neuronal Subtypes: A Biological Tool for Developmental Neurotoxicity Studies. Journal of Ecophysiology and Occupational Health, 18(3-4), 59–65. https://doi.org/10.18311/jeoh/2018/17925
Received 2017-08-28
Accepted 2019-01-30
Published 2019-01-30

 

References

Aboody K, Capela A, Niazi N, Stern JH, Temple S. Translating stem cell studies to the clinic for CNS repair: current state of the art and the need for a Rosetta stone. Neuron. 2011; 70(4): 597–613. https://doi.org/10.1016/j.neuron.2011.05.007. PMid:21609819.

Rossi F, Cattaneo E. Opinion: neural stem cell therapy for neurological diseases: dreams and reality. Nature Reviews Neuroscience. 2002; 3(5): 401–409. https://doi.org/10.1038/nrn809. PMid:11988779.

Kempermann G, Jessberger S, Steiner B, Kronenberg G. Milestones of neuronal development in the adult hippocampus. Trends in Neurosciences. 2004; 27(8): 447–52. https://doi.org/10.1016/j.tins.2004.05.013. PMid:15271491.

Ming G-l, Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011; 70(4): 687–702. https://doi.org/10.1016/j.neuron.2011.05.001. PMid:21609825 PMCid:PMC3106107.

Gage FH. Mammalian neural stem cells. Science. 2000; 287 (5457): 1433–38. https://doi.org/10.1126/science.287.5457.1433. PMid:10688783.

Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992; 255(5052): 1707–10. https://doi.org/10.1126/science.1553558.

Konagaya S, Kato K, Nakaji-Hirabayashi T, Arima Y, Iwata H. Array-based functional screening of growth factors toward optimizing neural stem cell microenvironments. Biomaterials. 2011; 32(22): 5015–22. https://doi.org/10.1016/j.biomaterials.2011.03.066. PMid:21513976.

Moyse E, Segura S, Liard O, Mahaut S, Mechawar N. Microenvironmental determinants of adult neural stem cell proliferation and lineage commitment in the healthy and injured central nervous system. Current Stem Cell Research & Therapy. 2008; 3(3): 163–184. https://doi.org/10.2174/157488808785740334.

Wang F-w, Hao H-b, Zhao S-d, Zhang Y-m, Liu Q, Liu H-j, et al. Roles of activated astrocyte in neural stem cell proliferation and differentiation. Stem Cell Research. 2011; 7(1): 41–53. https://doi.org/10.1016/j.scr.2011.03.004. PMid:21530437.

Huang YJ, Wu HC, Tai NH, Wang TW. Carbon nanotube rope with electrical stimulation promotes the differentiation and maturity of neural stem cells. Small. 2012; 8(18): 2869–77. https://doi.org/10.1002/smll.201200715. PMid:22753249.

Rossi F, Cattaneo E. Opinion: neural stem cell therapy for neurological diseases: dreams and reality. Nature Reviews Neuroscience. 2002; 3(5): 401–409. https://doi.org/10.1038/nrn809. PMid:11988779.

Blesch A, Lu P, Tuszynski MH. Neurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain Research Bulletin. 2002; 57(6): 833–38. https://doi.org/10.1016/S03619230(01)00774-2.

Jahan S, Kumar D, Kumar A, Rajpurohit CS, Singh S, Srivastava A, et al. Neurotrophic factor mediated neuronal differentiation of human cord blood mesenchymal stem cells and their applicability to assess the developmental neurotoxicity. Biochemical and Biophysical Research Communications. 2017; 482(4): 961–67. https://doi.org/10.1016/j.bbrc.2016.11.140. PMid:27899317.

Kumar V, Pandey A, Jahan S, Shukla RK, Kumar D, Srivastava A, et al. Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis. Scientific Reports. 2016; 6: 28142. https://doi.org/10.1038/srep28142. PMid:27334554. PMCid:PMC4917886.

Kumar V, Gupta AK, Shukla RK, Tripathi VK, Jahan S, Pandey A, et al. Molecular Mechanism of Switching of TrkA/p75NTR Signaling in Monocrotophos Induced Neurotoxicity. Scientific Reports. 2015; 5: 14038. https://doi.org/10.1038/srep14038. PMid:26370177. PMCid:PMC4570211.

Orlacchio A, Bernardi G, Martino S. Stem cells: an overview of the current status of therapies for central and peripheral nervous system diseases. Current Medicinal Chemistry. 2010; 17(7): 595–608. https://doi.org/10.2174/092986710790416272. PMid:20088765.

Singh S, Srivastava A, Kumar V, Pandey A, Kumar D, Rajpurohit C, et al. Stem cells in neurotoxicology/developmental neurotoxicology: current scenario and future prospects. Molecular Neurobiology. 2016; 53(10): 6938–49. https://doi.org/10.1007/s12035-015-9615-2. PMid:26666665.

Tarasenko YI, Yu Y, Jordan PM, Bottenstein J, Wu P. Effect of growth factors on proliferation and phenotypic differentiation of human fetal neural stem cells. Journal of Neuroscience Research. 2004; 78(5): 625–36. https://doi.org/10.1002/jnr.20316. PMid:15490463.

Faigle R, Song H. Signaling mechanisms regulating adult neural stem cells and neurogenesis. Biochimica et Biophysica Acta (BBA)-General Subjects. 2013; 1830(2): 2435–48. https://doi.org/10.1016/j.bbagen.2012.09.002. PMid:22982587. PMCid:PMC3541438.

Hagag N, Halegoua S, Viola M. Inhibition of growth factorinduced differentiation of PC12 cells by microinjection of antibody to ras p21. Nature. 1986; 319(6055): 680–82. https://doi.org/10.1038/319680a0. PMid:3005866.

Gomez"Santos C, Ferrer I, Santidrian AF, Barrachina M, Gil J, Ambrosio S. Dopamine induces autophagic cell death and α" synuclein increase in human neuroblastoma SH"SY5Y cells. Journal of Neuroscience Research. 2003; 73(3): 341–50. https://doi.org/10.1002/jnr.10663. PMid:12868068.