The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells
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Damage to the nervous system can be caused by several types of insults, and it always has a great effect on the life of an individual. Due to the limited availability of neural transplants, alternative approaches for neural regeneration must be developed. Stem cells have a great potential to support neuronal regeneration. Human adipose-derived stem cells (hADSCs) have gained increasing interest in the fields of regenerative medicine due to their multilineage potential and easy harvest compared to other stem cells. In this study, we present a growth factor-free method for the differentiation of hADSCs toward neuron-like cells. We investigated the effect of electric current and copper on neuronal differentiation. We analyzed the morphological changes, the mRNA and protein expression levels in the stimulated cells and showed that the combination of current and copper induces stem cell differentiation toward the neuronal lineage with elongation of the cells and the upregulation of neuron-specific genes and proteins. The induction of the neuronal differentiation of hADSCs by electric field and copper may offer a novel approach for stem cell differentiation and may be a useful tool for safe stem cell-based therapeutic applications.
KeywordsAdipose-derived stem cell Electric current Copper Differentiation Neurons
This work was mainly funded by the Finnish Cultural Foundation. The work was performed in the Laboratory of Biosensors and Bioelectronics at the ETH Zurich, Switzerland and we are most grateful of their scientific and financial support.
- 1.Abrous, D. N., M. Koehl, and M. L. E. Moal. Adult neurogenesis: from precursors to network and physiology. Physiol. Rev., 523–569, 2005. doi: 10.1152/physrev.00055.2003.
- 6.Choi, S. A., J. Y. Lee, K.-C. Wang, J. H. Phi, S. H. Song, J. Song, and S.-K. Kim. Human adipose tissue-derived mesenchymal stem cells: characteristics and therapeutic potential as cellular vehicles for prodrug gene therapy against brainstem gliomas. Eur. J. Cancer 48:129–137, 2012.CrossRefPubMedGoogle Scholar
- 8.Gutierrez-Aranda, I., V. Ramos-Mejia, C. Bueno, M. Munoz-Lopez, P. J. Real, A. Mácia, L. Sanchez, G. Ligero, J. L. Garcia-Parez, and P. Menendez. Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells 28:1568–1570, 2010.CrossRefPubMedCentralPubMedGoogle Scholar
- 19.Krampera, M., S. Marconi, A. Pasini, M. Galiè, G. Rigotti, F. Mosna, M. Tinelli, L. Lovato, E. Anghileri, A. Andreini, G. Pizzolo, A. Sbarbati, and B. Bonetti. Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus. Bone 40:382–390, 2007.CrossRefPubMedGoogle Scholar
- 20.Lebonvallet, N., N. Boulais, C. Le Gall, J. Chéret, U. Pereira, O. Mignen, V. Bardey, C. Jeanmaire, L. Danoux, G. Pauly, and L. Misery. Characterization of neurons from adult human skin-derived precursors in serum-free medium : a PCR array and immunocytological analysis. Exp. Dermatol. 21:195–200, 2012.CrossRefPubMedGoogle Scholar
- 28.Neuhuber, B., G. Gallo, L. Howard, L. Kostura, A. Mackay, and I. Fischer. Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype. J. Neurosci. Res. 77:192–204, 2004.CrossRefPubMedGoogle Scholar
- 37.Serena, E., E. Figallo, N. Tandon, C. Cannizzaro, S. Gerecht, N. Elvassore, and G. Vunjak-Novakovic. Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species. Exp. Cell Res. 315:3611–3619, 2009.CrossRefPubMedCentralPubMedGoogle Scholar
- 38.Tandon, N., B. Goh, A. Marsano, P.-H. G. Chao, C. Montouri-Sorrentino, J. Gimble, and G. Vunjak-Novakovic. Alignment and elongation of human adipose-derived stem cells in response to direct-current electrical stimulation. Conference Proceedings of IEEE Engineering in Medicine and Biological Society, 2009, pp. 6517–6521.Google Scholar
- 39.Tandon, N., E. Cimetta, A. Villasante, N. Kupferstein, M. D. Southall, A. Fassih, J. Xie, Y. Sun, and G. Vunjak-Novakovic. Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathway. Exp. Cell Res. 320:79–91, 2014.CrossRefPubMedGoogle Scholar
- 41.Titushkin, I. A, and M. R. Cho. Controlling cellular biomechanics of human mesenchymal stem cells. Conference Proceedings of IEEE Engineering in Medicine and Biology Society 2009, pp. 2090–2093.Google Scholar
- 43.Yamada, M., K. Tanemura, S. Okada, A. Iwanami, M. Nakamura, H. Mizuno, M. Ozawa, R. Ohyama-Goto, N. Kitamura, M. Kawano, K. Tan-Takeuchi, C. Ohtsuka, A. Miyawaki, A. Takashima, M. Ogawa, Y. Toyama, H. Okano, and T. Kondo. Electrical stimulation modulates fate determination of differentiating embryonic stem cells. Stem Cells 25:562–570, 2007.CrossRefPubMedGoogle Scholar