Electrical Stimulation Modulates Fate Determination of Differentiating Embryonic Stem Cells

A clear understanding of cell fate regulation during differentiation is key in successfully using stem cells for therapeutic applications. Here, we report that mild electrical stimulation strongly influences embryonic stem cells to assume a neuronal fate. Although the resulting neuronal cells showed no sign of specific terminal differentiation in culture, they showed potential to differentiate into various types of neurons in vivo, and, in adult mice, contributed to the injured spinal cord as neuronal cells. Induction of calcium ion influx is significant in this differentiation system. This phenomenon opens up possibilities for understanding novel mechanisms underlying cellular differentiation and early development, and, perhaps more importantly, suggests possibilities for treatments in medical contexts.

[1]  H. Okano,et al.  Transplantation of in vitro‐expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats , 2002, Journal of neuroscience research.

[2]  H. Okano,et al.  Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury , 2007, Journal of neuroscience research.

[3]  A. West,et al.  Calcium regulation of neuronal gene expression , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Masaya Nakamura,et al.  Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord , 2003, Experimental Neurology.

[5]  G. Crabtree,et al.  NFAT Signaling Choreographing the Social Lives of Cells , 2002, Cell.

[6]  K. Mizuseki,et al.  Induction of Midbrain Dopaminergic Neurons from ES Cells by Stromal Cell–Derived Inducing Activity , 2000, Neuron.

[7]  T. Jessell,et al.  Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes , 1994, Cell.

[8]  T. Gratsch,et al.  Noggin and chordin have distinct activities in promoting lineage commitment of mouse embryonic stem (ES) cells. , 2002, Developmental biology.

[9]  Hideyuki Okano,et al.  Establishment of three-dimensional culture of neural stem/progenitor cells in collagen Type-1 Gel. , 2007, Restorative neurology and neuroscience.

[10]  B. Bregman,et al.  Differences in Neurotrophic Factor Gene Expression Profiles between Neonate and Adult Rat Spinal Cord after Injury , 2001, Experimental Neurology.

[11]  Janet Rossant,et al.  Direct Neural Fate Specification from Embryonic Stem Cells A Primitive Mammalian Neural Stem Cell Stage Acquired through a Default Mechanism , 2001, Neuron.

[12]  Yamamura Ken-ichi,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector , 1991 .

[13]  Han-Woong Lee,et al.  Dynamic rearrangement of telomeres during spermatogenesis in mice. , 2005, Developmental biology.

[14]  N. Spitzer,et al.  Orchestrating neuronal differentiation: patterns of Ca2+ spikes specify transmitter choice , 2004, Trends in Neurosciences.

[15]  H. Okano,et al.  Nestin enhancer requirements for expression in normal and injured adult CNS , 2002, Journal of neuroscience research.

[16]  K. Tsubota,et al.  Topography-guided ablation for treatment of patients with irregular astigmatism. , 2006, Journal of refractive surgery.

[17]  Marius Wernig,et al.  In vitro differentiation of transplantable neural precursors from human embryonic stem cells , 2001, Nature Biotechnology.

[18]  K. Tsubota,et al.  Barrier function and cytologic features of the ocular surface epithelium after autologous cultivated oral mucosal epithelial transplantation. , 2008, Archives of ophthalmology.

[19]  R. McKay,et al.  Embryonic stem cell-derived glial precursors: a source of myelinating transplants. , 1999, Science.

[20]  H. Wichterle,et al.  Directed Differentiation of Embryonic Stem Cells into Motor Neurons , 2002, Cell.

[21]  M. Kühl,et al.  Increasingly complex: new players enter the Wnt signaling network. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  Y. Itoyama,et al.  Disease progression of human SOD1 (G93A) transgenic ALS model rats , 2006, Journal of neuroscience research.

[23]  Y. Toyama,et al.  Synaptic blockade plays a major role in the neural disturbance of experimental spinal cord compression. , 2003, Journal of neurotrauma.

[24]  G. Lyons,et al.  In vitro chamber specification during embryonic stem cell cardiogenesis. Expression of the ventricular myosin light chain-2 gene is independent of heart tube formation. , 1993, The Journal of biological chemistry.

[25]  T. Jessell,et al.  Specification of Motor Neuron Identity by the MNR2 Homeodomain Protein , 1998, Cell.

[26]  Peter Gruss,et al.  Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid , 1991, Cell.

[27]  H. Okano,et al.  Neutralization of ciliary neurotrophic factor reduces astrocyte production from transplanted neural stem cells and promotes regeneration of corticospinal tract fibers in spinal cord injury , 2006, Journal of neuroscience research.

[28]  Takeharu Nagai,et al.  Shift anticipated in DNA microarray market , 2002, Nature Biotechnology.

[29]  Jonas Frisén,et al.  Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System , 1999, Cell.

[30]  Austin G Smith,et al.  Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture , 2003, Nature Biotechnology.

[31]  W. Young,et al.  Endogenous Repair after Spinal Cord Contusion Injuries in the Rat , 1997, Experimental Neurology.

[32]  T. Shimazaki,et al.  Blockade of interleukin‐6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury , 2004, Journal of neuroscience research.

[33]  T. Shimazaki,et al.  Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis and functional recovery , 2004, Journal of neuroscience research.

[34]  岩波 明生.  Transplantation of human neural stem cells for spinal cord injury in primates , 2005 .

[35]  H. Nakae.  Morphological differentiation of rat pheochromocytoma cells (PC12 cells) by electric stimulation , 1991, Brain Research.

[36]  K. Tsubota,et al.  Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease , 2008, Bone Marrow Transplantation.

[37]  H. Okano,et al.  Comparison between Fetal Spinal-Cord- and Forebrain-Derived Neural Stem/Progenitor Cells as a Source of Transplantation for Spinal Cord Injury , 2004, Developmental Neuroscience.

[38]  Min Zhao,et al.  Has electrical growth cone guidance found its potential? , 2002, Trends in Neurosciences.

[39]  Li I. Zhang,et al.  Electrical activity and development of neural circuits , 2001, Nature Neuroscience.

[40]  C. Contag,et al.  In vivo imaging of engrafted neural stem cells: its application in evaluating the optimal timing of transplantation for spinal cord injury , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[41]  K. Tsubota,et al.  Postkeratoplasty atopic sclerokeratitis in keratoconus patients. , 2008, Ophthalmology.

[42]  J. Kouril,et al.  SHORT COMMUNICATION , 2004, Aquaculture International.

[43]  Hideyuki Okano,et al.  Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury , 2006, Nature Medicine.

[44]  R. Moon,et al.  Ca2+/Calmodulin-dependent Protein Kinase II Is Stimulated by Wnt and Frizzled Homologs and Promotes Ventral Cell Fates in Xenopus* , 2000, The Journal of Biological Chemistry.

[45]  H. Okano.  Stem cell biology of the central nervous system , 2002, Journal of neuroscience research.

[46]  M. Yamada,et al.  Brain-Derived Neurotrophic Factor Promotes the Maturation of GABAergic Mechanisms in Cultured Hippocampal Neurons , 2002, The Journal of Neuroscience.

[47]  S. Manivannan,et al.  Rapid sprouting of filopodia in nerve terminals of chromaffin cells, PC12 cells, and dorsal root neurons induced by electrical stimulation , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  R. McKay,et al.  Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells , 2000, Nature Biotechnology.

[49]  R. McKay,et al.  Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets , 2001, Science.

[50]  H. Niwa,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector. , 1991, Gene.

[51]  E. Coucouvanis,et al.  BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo. , 1999, Development.

[52]  H. Okano,et al.  In Vivo Tracing of Neural Tracts in the Intact and Injured Spinal Cord of Marmosets by Diffusion Tensor Tractography , 2007, The Journal of Neuroscience.

[53]  C. Cohan.  Frequency-dependent and cell-specific effects of electrical activity on growth cone movements of cultured Helisoma neurons. , 1990, Journal of neurobiology.

[54]  T Nomura,et al.  Establishment of graded spinal cord injury model in a nonhuman primate: The common marmoset , 2005, Journal of neuroscience research.

[55]  Y. Toyama,et al.  Spinal kyphosis causes demyelination and neuronal loss in the spinal cord: a new model of kyphotic deformity using juvenile Japanese small game fowls. , 2014, Spine.

[56]  Takuji Ishikawa,et al.  Simulation of platelet adhesion and aggregation regulated by fibrinogen and von Willebrand factor , 2007, Thrombosis and Haemostasis.

[57]  Y. Toyama,et al.  Transplantation of neural stem cells into the spinal cord after injury. , 2003, Seminars in cell & developmental biology.

[58]  Karl Deisseroth,et al.  Excitation-Neurogenesis Coupling in Adult Neural Stem/Progenitor Cells , 2004, Neuron.

[59]  A. Miyawaki,et al.  Multicolor imaging of Ca(2+) and protein kinase C signals using novel epifluorescence microscopy. , 2002, Biophysical journal.