Open Access
Issue
Published:
19 October 2019
Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks
),
Download citation
595
Views
7
Downloads
26
Crossref
N/A
WoS
24
Scopus
0
CSCD
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.
menu
Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks
),
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.
References(32)
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.
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.
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.
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.
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.
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. Methods 2010, 7, 733–736.
Turney, S. G.; Bridgman, P. C. Laminin stimulates and guides axonal outgrowth via growth cone myosin Ⅱ activity. Nat. Neurosci. 2005, 8, 717–719.
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.
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.
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.
Kostarelos, K.; Bianco, A.; Prato, M. Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat. Nanotechnol. 2009, 4, 627–633.
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.
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.
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. Biomaterials 2012, 33, 4818–4827.
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. Langmuir 2012, 28, 17363–17371.
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.
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 Nano 2012, 6, 2041–2055.
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 Nano 2013, 7, 2369–2380.
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 Nano 2012, 6, 362–372.
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 Nano 2014, 8, 11958–11965.
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.
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.
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. Interfaces 2019, 11, 22152–22163.
Barrejón, M.; Rauti, R.; Ballerini, L.; Prato, M. Chemically cross-linked carbon nanotube films engineered to control neuronal signaling. ACS Nano 2019, 13, 8879–8889.
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.
Suzuki, I. K.; Vanderhaeghen, P. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells. Development 2015, 142, 3138–3150.
Avior, Y.; Sagi, I.; Benvenisty, N. Pluripotent stem cells in disease modelling and drug discovery. Nat. Rev. Mol. Cell Biol. 2016, 17, 170–182.
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.
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.
Discher, D. E.; Janmey, P.; Wang, Y. L. Tissue cells feel and respond to the stiffness of their substrate. Science 2005, 310, 1139–1143.
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.
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. Neuroscience 2011, 192, 793–805.
Publication history
Copyright
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.
Rights and permissions
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/.
FEEDBACK 
TOP