The influence of piezoelectric scaffolds on neural differentiation of human neural stem/progenitor cells.

Human neural stem/progenitor cells (hNSCs/NPCs) are a promising cell source for neural tissue engineering because of their ability to differentiate into various neural lineages. In this study, hNSC/NPC differentiation was evaluated on piezoelectric, fibrous scaffolds. These smart materials have an intrinsic material property where transient electric potential can be generated in the material upon minute mechanical deformation. hNSCs/NPCs cultured on the scaffolds and films differentiated into β-III tubulin-positive cells, a neuronal cell marker, with or without the presence of inductive factors. In contrast, hNSCs/NPCs cultured on laminin-coated plates were predominantly nestin positive, a NSC marker, in the control medium. Gene expression results suggest that the scaffolds may have promoted the formation of mature neural cells exhibiting neuron-like characteristics. hNSCs/NPCs differentiated mostly into β-III tubulin-positive cells and had the greatest average neurite length on micron-sized, annealed (more piezoelectric), aligned scaffolds, demonstrating their potential for neural tissue-engineering applications.

[1]  L. Vargova,et al.  Heterogeneous PHPMA hydrogels for tissue repair and axonal regeneration in the injured spinal cord. , 1998, Journal of biomaterials science. Polymer edition.

[2]  Charles Tator,et al.  Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection. , 2004, Journal of neurotrauma.

[3]  F. Gage.  Discussion point Stem cells of the central nervous system , 1998, Current Opinion in Neurobiology.

[4]  Nic D. Leipzig,et al.  The effect of substrate stiffness on adult neural stem cell behavior. , 2009, Biomaterials.

[5]  A. Patlolla,et al.  Solvent-dependent properties of electrospun fibrous composites for bone tissue regeneration. , 2010, Acta biomaterialia.

[6]  J. A. de Saja,et al.  Tailoring the structural properties of PVDF and P(VDF-TrFE) by using natural polymers as additives , 2009 .

[7]  Younan Xia,et al.  Neurite outgrowth on nanofiber scaffolds with different orders, structures, and surface properties. , 2009, ACS nano.

[8]  V. Baekelandt,et al.  Concise Review: Therapeutic Strategies for Parkinson Disease Based on the Modulation of Adult Neurogenesis , 2007, Stem cells.

[9]  J. Mcdonald,et al.  Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord , 1999, Nature Medicine.

[10]  E. Snyder,et al.  Human neurospheres derived from the fetal central nervous system are regionally and temporally specified but are not committed , 2006, Experimental Neurology.

[11]  Lauren Flynn,et al.  Fiber templating of poly(2-hydroxyethyl methacrylate) for neural tissue engineering. , 2003, Biomaterials.

[12]  R F Valentini,et al.  Electrically charged polymeric substrates enhance nerve fibre outgrowth in vitro. , 1992, Biomaterials.

[13]  Hongjun Song,et al.  The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation. , 2009, Biomaterials.

[14]  Charles Tator,et al.  Matrix inclusion within synthetic hydrogel guidance channels improves specific supraspinal and local axonal regeneration after complete spinal cord transection. , 2006, Biomaterials.

[15]  M. Oblinger,et al.  Differential regulation of beta III and other tubulin genes during peripheral and central neuron development. , 1992, Journal of cell science.

[16]  Xiaoyan Yuan,et al.  Preparation and properties of electrospun poly(vinylidene fluoride) membranes , 2005 .

[17]  D. Brown,et al.  Expression and posttranslational modification of class III beta-tubulin during neuronal differentiation of P19 embryonal carcinoma cells. , 1996, Cell motility and the cytoskeleton.

[18]  Molly S. Shoichet,et al.  Hydrogel/electrospun fiber composites influence neural stem/progenitor cell fate , 2010 .

[19]  M. Tuszynski,et al.  Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury , 2001, The Journal of physiology.

[20]  M. Poo,et al.  Perturbation of the direction of neurite growth by pulsed and focal electric fields , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  David F Meaney,et al.  Matrices with compliance comparable to that of brain tissue select neuronal over glial growth in mixed cortical cultures. , 2006, Biophysical journal.

[22]  F. Gage,et al.  Mammalian neural stem cells. , 2000, Science.

[23]  R. Franco-Bourland,et al.  Development of post-traumatic cysts in the spinal cord of rats-subjected to severe spinal cord contusion. , 1994, Surgical neurology.

[24]  P. Sykacek,et al.  Gene expression changes in long term expanded human neural progenitor cells passaged by chopping lead to loss of neurogenic potential in vivo , 2007, Experimental Neurology.

[25]  Zuzana Dobbie,et al.  Processing of gene expression data generated by quantitative real-time RT-PCR. , 2002, BioTechniques.

[26]  M. Fehlings,et al.  Delayed Transplantation of Adult Neural Precursor Cells Promotes Remyelination and Functional Neurological Recovery after Spinal Cord Injury , 2006, The Journal of Neuroscience.

[27]  A. Frankfurter,et al.  Class III β‐Tubulin isotype (β III) in the adrenal medulla: I. Localization in the developing human adrenal medulla , 1998 .

[28]  Aqing Chen,et al.  Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord , 1997, Journal of neurocytology.

[29]  G W Plant,et al.  Long-Distance Axonal Regeneration in the Transected Adult Rat Spinal Cord Is Promoted by Olfactory Ensheathing Glia Transplants , 1998, The Journal of Neuroscience.

[30]  P. Black,et al.  Targeting of melanoma brain metastases using engineered neural stem/progenitor cells. , 2006, Neuro-oncology.

[31]  Huanxing Su,et al.  Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord , 2007, Experimental Neurology.

[32]  J. de Vellis,et al.  Prevention of gliotic scar formation by NeuroGel™ allows partial endogenous repair of transected cat spinal cord , 2004, Journal of neuroscience research.

[33]  P. Aebischer,et al.  Regrowth of axons into the distal spinal cord through a Schwann‐cell‐seeded mini‐channel implanted into hemisected adult rat spinal cord , 1999, The European journal of neuroscience.

[34]  Zhengang Yang,et al.  Neural Stem/Progenitor Cells Participate in the Regenerative Response to Perinatal Hypoxia/Ischemia , 2006, The Journal of Neuroscience.

[35]  Albert J. Keung,et al.  Substrate modulus directs neural stem cell behavior. , 2008, Biophysical journal.

[36]  S. Blanchard,et al.  Directed Evolution of Motor Neurons from Genetically Engineered Neural Precursors , 2008, Stem cells.

[37]  J. Silver,et al.  CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure , 2008, Experimental Neurology.

[38]  R. Pallini,et al.  Acrylic hydrogel implants after spinal cord lesion in the adult rat , 2001, Neurological research.

[39]  Charles Tator,et al.  Bioengineered strategies for spinal cord repair. , 2006, Journal of neurotrauma.

[40]  M. Rao,et al.  Properties of a fetal multipotent neural stem cell (NEP cell). , 2002, Developmental biology.

[41]  D. Moran,et al.  Conductive Core–Sheath Nanofibers and Their Potential Application in Neural Tissue Engineering , 2009, Advanced functional materials.

[42]  Rivelino Montenegro,et al.  Coil-reinforced hydrogel tubes promote nerve regeneration equivalent to that of nerve autografts. , 2006, Biomaterials.

[43]  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.

[44]  George Collins,et al.  Neurite extension of primary neurons on electrospun piezoelectric scaffolds. , 2011, Acta biomaterialia.

[45]  Nobuko Uchida,et al.  Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[46]  A. Harvey,et al.  The Regrowth of Axons within Tissue Defects in the CNS Is Promoted by Implanted Hydrogel Matrices That Contain BDNF and CNTF Producing Fibroblasts , 2001, Experimental Neurology.

[47]  C. Montoliu,et al.  Developmental pattern of GFAP and vimentin gene expression in rat brain and in radial glial cultures , 1995, Glia.

[48]  Y. Liu,et al.  Co‐transplantation of bFGF‐expressing amniotic epithelial cells and neural stem cells promotes functional recovery in spinal cord‐injured rats , 2008, Cell biology international.

[49]  Jens Friedrichs,et al.  Cellular remodelling of individual collagen fibrils visualized by time-lapse AFM. , 2007, Journal of molecular biology.

[50]  T. Arinzeh,et al.  Characterization and in vitro cytocompatibility of piezoelectric electrospun scaffolds. , 2010, Acta biomaterialia.

[51]  S. Woerly,et al.  Polymer hydrogels usable for nervous tissue repair , 2002, Journal of Chemical Neuroanatomy.

[52]  S. Whittemore,et al.  Functional considerations of stem cell transplantation therapy for spinal cord repair. , 2006, Journal of neurotrauma.

[53]  K. Khalili,et al.  Class III &bgr;-Tubulin Is Constitutively Coexpressed With Glial Fibrillary Acidic Protein and Nestin in Midgestational Human Fetal Astrocytes: Implications for Phenotypic Identity , 2008, Journal of neuropathology and experimental neurology.

[54]  J. Rothstein,et al.  Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[55]  M. Rao,et al.  Stem cell therapy in multiple sclerosis: promise and controversy , 2008, Multiple sclerosis.

[56]  C. Scharff,et al.  Gene Expression Changes in the Course of Neural Progenitor Cell Differentiation , 2022 .

[57]  J. Runt,et al.  P(VDF-TrFE)-layered silicate nanocomposites. Part 1. X-ray scattering and thermal analysis studies , 2004 .

[58]  M. Coutts,et al.  Stem cells for treatment of spinal cord injury , 2008, Experimental Neurology.

[59]  R. McKay,et al.  Stem Cells in the Central Nervous System , 1997, Science.

[60]  R. McKay,et al.  A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. , 2002, Genes & development.

[61]  Lauren Flynn,et al.  Manufacture of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) hydrogel tubes for use as nerve guidance channels. , 2002, Biomaterials.

[62]  Jennifer T. Blundo,et al.  In vivo imaging and evaluation of different biomatrices for improvement of stem cell survival , 2007, Journal of tissue engineering and regenerative medicine.

[63]  G. Bowlin,et al.  Scaffold permeability as a means to determine fiber diameter and pore size of electrospun fibrinogen. , 2008, Journal of biomedical materials research. Part A.

[64]  Andreas Greiner,et al.  Electrospinning: a fascinating method for the preparation of ultrathin fibers. , 2007, Angewandte Chemie.

[65]  Xiao-Ming Xu,et al.  Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury , 2003, Experimental Neurology.

[66]  G. Martino,et al.  The therapeutic potential of neural stem cells , 2006, Nature Reviews Neuroscience.