Advertisement

Nano Research

, Volume 12, Issue 11, pp 2894–2899 | Cite as

Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks

  • Gabriela S. LoriteEmail author
  • Laura Ylä-Outinen
  • Lauriane Janssen
  • Olli Pitkänen
  • Tiina Joki
  • Janne T. Koivisto
  • Minna Kellomäki
  • Robert Vajtai
  • Susanna Narkilahti
  • Krisztian Kordas
Open Access
Research Article

Abstract

New strategies for spatially controlled growth of human neurons may provide viable solutions to treat and recover peripheral or spinal cord injuries. While topography cues are known to promote attachment and direct proliferation of many cell types, guided outgrowth of human neurites has been found difficult to achieve so far. Here, three-dimensional (3D) micropatterned carbon nanotube (CNT) templates are used to effectively direct human neurite stem cell growth. By exploiting the mechanical flexibility, electrically conductivity and texture of the 3D CNT micropillars, a perfect environment is created to achieve specific guidance of human neurites, which may lead to enhanced therapeutic effects within the injured spinal cord or peripheral nerves. It is found that the 3D CNT micropillars grant excellent anchoring for adjacent neurites to form seamless neuronal networks that can be grown to any arbitrary shape and size. Apart from clear practical relevance in regenerative medicine, these results using the CNT based templates on Si chips also can pave the road for new types of microelectrode arrays to study cell network electrophysiology.

Keywords

carbon nanotubes multiple cues guided neurite outgrowth human neural stem cells neuronal networks 

Notes

Acknowledgements

G. S. L. and L. Y-O. acknowledge the support from the Academy of Finland (Nos. 320090, 317437 and 286990, respectively). J. T. K. and T. J. acknowledge the support from the Finnish Cultural Foundation Pirkanmaa Regional Fund (No. 50151501) and the Central Fund (#00150312), respectively. S. N., T. J. and M. K. acknowledge the support from the Academy of Finland (S. N. and T. J. No. 312414 and M. K. No. 312409) and Business Finland (former Tekes, Human Spare Parts project). This work made use of the electron microscopy and clean-room facilities at the Centre of Microscopy and Nanotechnology, at the University of Oulu. The authors also acknowledge the Tampere Imaging Facility (TIF) and the Tampere CellTech Laboratories for their service.

Funding: Open access funding provided by University of Oulu including Oulu University Hospital.

Supplementary material

12274_2019_2533_MOESM1_ESM.pdf (4 mb)
Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks
12274_2019_2533_MOESM2_ESM.mp4 (83 mb)
Supplementary material, approximately 83.0 MB.

References

  1. [1]
    Lowery, L. A.; van Vactor, D. The trip of the tip: Understanding the growth cone machinery. Nat. Rev. Mol. Cell Biol.2009, 10, 332–343.CrossRefGoogle Scholar
  2. [2]
    Simitzi, C.; Ranella, A.; Stratakis, E. Controlling the morphology and outgrowth of nerve and neuroglial cells: The effect of surface topography. Acta Biomater.2017, 51, 21–52.CrossRefGoogle Scholar
  3. [3]
    Li, W.; Tang, Q. Y.; Jadhav, A. D.; Narang, A.; Qian, W. X.; Shi, P.; Pang, S. W. Large-scale topographical screen for investigation of physical neural-guidance cues. Sci. Rep.2015, 5, 8644.CrossRefGoogle Scholar
  4. [4]
    Solanki, A.; Chueng, S. T. D.; Yin, P. T.; Kappera, R.; Chhowalla, M.; Lee, K. B. Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures. Adv. Mater.2013, 25, 5477–5482.CrossRefGoogle Scholar
  5. [5]
    Hyysalo, A.; Ristola, M.; Joki, T.; Honkanen, M.; Vippola, M.; Narkilahti, S. Aligned poly(ε-caprolactone) nanofibers guide the orientation and migration of human pluripotent stem cell-derived neurons, astrocytes, and oligodendrocyte precursor cells in vitro. Macromol. Biosci.2017, 17, 1600517.CrossRefGoogle Scholar
  6. [6]
    Fu, J. P.; Wang, Y. K.; Yang, M. T.; Desai, R. A.; Yu, X.; Liu, Z. J.; Chen, C. S. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat. Methods2010, 7, 733–736.CrossRefGoogle Scholar
  7. [7]
    Turney, S. G.; Bridgman, P. C. Laminin stimulates and guides axonal outgrowth via growth cone myosin II activity. Nat. Neurosci.2005, 8, 717–719.CrossRefGoogle Scholar
  8. [8]
    Millaruelo, A. I.; Nieto-Sampedro, M.; Cotman, C. W. Cooperation between nerve growth factor and laminin or fibronectin in promoting sensory neuron survival and neurite outgrowth. Dev. Brain Res.1988, 38, 219–228.CrossRefGoogle Scholar
  9. [9]
    Hammarback, J. A.; Palm, S. L.; Furcht, L. T.; Letourneau, P. C. Guidance of neurite outgrowth by pathways of substratum-adsorbed laminin. J. Neurosci. Res.1985, 13, 213–220.CrossRefGoogle Scholar
  10. [10]
    Gundersen, R. W. Response of sensory neurites and growth cones to patterned substrata of laminin and fibronectin in vitro. Dev. Biol.1987, 121, 423–431.CrossRefGoogle Scholar
  11. [11]
    Kostarelos, K.; Bianco, A.; Prato, M. Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat. Nanotechnol.2009, 4, 627–633.CrossRefGoogle Scholar
  12. [12]
    Zhang, B. B.; Yan, W.; Zhu, Y. J.; Yang, W. T.; Le, W. J.; Chen, B. D.; Zhu, R. R.; Cheng, L. M. Nanomaterials in neural-stem-cell-mediated regenerative medicine: Imaging and treatment of neurological diseases. Adv. Mater.2018, 30, 1705694.CrossRefGoogle Scholar
  13. [13]
    Besteman, K.; Lee, J. O.; Wiertz, F. G. M.; Heering, H. A.; Dekker, C. Enzyme-coated carbon nanotubes as single-molecule biosensors. Nano Lett.2003, 3, 727–730.CrossRefGoogle Scholar
  14. [14]
    Li, X. M.; Liu, H. F.; Niu, X. F.; Yu, B.; Fan, Y. B.; Feng, Q. L.; Cui, F. Z.; Watari, F. The use of carbon nanotubes to induce osteogenic differentiation of human adipose-derived MSCs in vitro and ectopic bone formation in vivo. Biomaterials2012, 33, 4818–4827.CrossRefGoogle Scholar
  15. [15]
    Béduer, A.; Seichepine, F.; Flahaut, E.; Loubinoux, I.; Vaysse, L.; Vieu, C. Elucidation of the role of carbon nanotube patterns on the development of cultured neuronal cells. Langmuir2012, 28, 17363–17371.CrossRefGoogle Scholar
  16. [16]
    Chao, T. I.; Xiang, S. H.; Lipstate, J. F.; Wang, C. C.; Lu, J. Poly(methacrylic acid)-grafted carbon nanotube scaffolds enhance differentiation of hESCs into neuronal cells. Adv. Mater.2010, 22, 3542–3547.CrossRefGoogle Scholar
  17. [17]
    Fabbro, A.; Villari, A.; Laishram, J.; Scaini, D.; Toma, F. M.; Turco, A.; Prato, M.; Ballerini, L. Spinal cord explants use carbon nanotube interfaces to enhance neurite outgrowth and to fortify synaptic inputs. ACS Nano2012, 6, 2041–2055.CrossRefGoogle Scholar
  18. [18]
    Shin, S. R.; Jung, S. M.; Zalabany, M.; Kim, K.; Zorlutuna, P.; Kim, S. B.; Nikkhah, M.; Khabiry, M.; Azize, M.; Kong, J. et al. Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators. ACS Nano2013, 7, 2369–2380.CrossRefGoogle Scholar
  19. [19]
    Shin, S. R.; Bae, H.; Cha, J. M.; Mun, J. Y.; Chen, Y. C.; Tekin, H.; Shin, H.; Farshchi, S.; Dokmeci, M. R.; Tang, S. et al. Carbon nanotube reinforced hybrid microgels as scaffold materials for cell encapsulation. ACS Nano2012, 6, 362–372.CrossRefGoogle Scholar
  20. [20]
    Xie, X.; Zhao, W. T.; Lee, H. R.; Liu, C.; Ye, M.; Xie, W. J.; Cui, B. X.; Criddle, C. S.; Cui, Y. Enhancing the nanomaterial bio-interface by addition of mesoscale secondary features: Crinkling of carbon nanotube films to create subcellular ridges. ACS Nano2014, 8, 11958–11965.CrossRefGoogle Scholar
  21. [21]
    Cellot, G.; Cilia, E.; Cipollone, S.; Rancic, V.; Sucapane, A.; Giordani, S.; Gambazzi, L.; Markram, H.; Grandolfo, M.; Scaini, D. et al. Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts. Nat. Nanotechnol.2009, 4, 126–133.CrossRefGoogle Scholar
  22. [22]
    Gheith, M. K.; Pappas, T. C.; Liopo, A. V.; Sinani, V. A.; Shim, B. S.; Motamedi, M.; Wicksted, J. P.; Kotov, N. A. Stimulation of neural cells by lateral currents in conductive layer-by-layer films of single-walled carbon nanotubes. Adv. Mater.2006, 18, 2975–2979.CrossRefGoogle Scholar
  23. [23]
    Wu, C. H.; Liu, A. M.; Chen, S. P.; Zhang, X. F.; Chen, L.; Zhu, Y. D.; Xiao, Z. W.; Sun, J.; Luo, H. R.; Fan, H. S. Cell-laden electroconductive hydrogel simulating nerve matrix to deliver electrical cues and promote neurogenesis. ACS Appl. Mater. Interfaces2019, 11, 22152–22163.CrossRefGoogle Scholar
  24. [24]
    Barrejón, M.; Rauti, R.; Ballerini, L.; Prato, M. Chemically cross-linked carbon nanotube films engineered to control neuronal signaling. ACS Nano2019, 13, 8879–8889.CrossRefGoogle Scholar
  25. [25]
    Zhang, X.; Prasad, S.; Niyogi, S.; Morgan, A.; Ozkan, M.; Ozkan, C. S. Guided neurite growth on patterned carbon nanotubes. Sens. Actuators B Chem.2005, 106, 843–850.CrossRefGoogle Scholar
  26. [26]
    Suzuki, I. K.; Vanderhaeghen, P. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells. Development2015, 142, 3138–3150.CrossRefGoogle Scholar
  27. [27]
    Avior, Y.; Sagi, I.; Benvenisty, N. Pluripotent stem cells in disease modelling and drug discovery. Nat. Rev. Mol. Cell Biol.2016, 17, 170–182.CrossRefGoogle Scholar
  28. [28]
    Kasteel, E. E. J.; Westerink, R. H. S. Comparison of the acute inhibitory effects of tetrodotoxin (TTX) in rat and human neuronal networks for risk assessment purposes. Toxicol. Lett.2017, 270, 12–16.CrossRefGoogle Scholar
  29. [29]
    Lovat, V.; Pantarotto, D.; Lagostena, L.; Cacciari, B.; Grandolfo, M.; Righi, M.; Spalluto, G.; Prato, M.; Ballerini, L. Carbon nanotube substrates boost neuronal electrical signaling. Nano Lett.2005, 5, 1107–1110.CrossRefGoogle Scholar
  30. [30]
    Discher, D. E.; Janmey, P.; Wang, Y. L. Tissue cells feel and respond to the stiffness of their substrate. Science2005, 310, 1139–1143.CrossRefGoogle Scholar
  31. [31]
    Ali, S.; Wall, I. B.; Mason, C.; Pelling, A. E.; Veraitch, F. S. The effect of Young’s modulus on the neuronal differentiation of mouse embryonic stem cells. Acta Biomater.2015, 25, 253–267.CrossRefGoogle Scholar
  32. [32]
    Young, A.; Machacek, D. W.; Dhara, S. K.; MacLeish, P. R.; Benveniste, M.; Dodla, M. C.; Sturkie, C. D.; Stice, S. L. Ion channels and ionotropic receptors in human embryonic stem cell derived neural progenitors. Neuroscience2011, 192, 793–805.CrossRefGoogle Scholar

Copyright information

© The Author(s) 2019

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Authors and Affiliations

  • Gabriela S. Lorite
    • 1
    Email author
  • Laura Ylä-Outinen
    • 2
  • Lauriane Janssen
    • 1
  • Olli Pitkänen
    • 1
  • Tiina Joki
    • 2
  • Janne T. Koivisto
    • 3
  • Minna Kellomäki
    • 3
  • Robert Vajtai
    • 4
  • Susanna Narkilahti
    • 2
  • Krisztian Kordas
    • 1
  1. 1.Microelectronics Research UnitUniversity of OuluOuluFinland
  2. 2.NeuroGroup, BioMediTech and Faculty of Medicine and Health technologyTampere UniversityTampereFinland
  3. 3.Biomaterials & Tissue Engineering Group, BioMediTech, Faculty of Medicine and Health TechnologyTampere UniversityTampereFinland
  4. 4.Department of Materials Science and NanoengineeringRice UniversityHoustonUSA

Personalised recommendations