Enhanced noradrenergic axon regeneration into schwann cell‐filled PVDF‐TrFE conduits after complete spinal cord transection

Schwann cell (SC) transplantation has been utilized for spinal cord repair and demonstrated to be a promising therapeutic strategy. In this study, we investigated the feasibility of combining SC transplantation with novel conduits to bridge the completely transected adult rat spinal cord. This is the first and initial study to evaluate the potential of using a fibrous piezoelectric polyvinylidene fluoride trifluoroethylene (PVDF‐TrFE) conduit with SCs for spinal cord repair. PVDF‐TrFE has been shown to enhance neurite growth in vitro and peripheral nerve repair in vivo. In this study, SCs adhered and proliferated when seeded onto PVDF‐TrFE scaffolds in vitro. SCs and PVDF‐TrFE conduits, consisting of random or aligned fibrous inner walls, were transplanted into transected rat spinal cords for 3 weeks to examine early repair. Glial fibrillary acidic protein (GFAP)+ astrocyte processes and GFP (green fluorescent protein)‐SCs were interdigitated at both rostral and caudal spinal cord/SC transplant interfaces in both types of conduits, indicative of permissivity to axon growth. More noradrenergic/DβH+ (dopamine‐beta‐hydroxylase) brainstem axons regenerated across the transplant when greater numbers of GFAP+ astrocyte processes were present. Aligned conduits promoted extension of DβH+ axons and GFAP+ processes farther into the transplant than random conduits. Sensory CGRP+ (calcitonin gene‐related peptide) axons were present at the caudal interface. Blood vessels formed throughout the transplant in both conduits. This study demonstrates that PVDF‐TrFE conduits harboring SCs are promising for spinal cord repair and deserve further investigation. Biotechnol. Bioeng. 2017;114: 444–456. © 2016 Wiley Periodicals, Inc.

[1]  M. Minary‐Jolandan,et al.  Thermo-electromechanical Behavior of Piezoelectric Nanofibers. , 2016, ACS applied materials & interfaces.

[2]  M. Soleimani,et al.  Co-transplantation of autologous bone marrow mesenchymal stem cells and Schwann cells through cerebral spinal fluid for the treatment of patients with chronic spinal cord injury: safety and possible outcome , 2015, Spinal Cord.

[3]  Michael Jaffe,et al.  Piezoelectric materials for tissue regeneration: A review. , 2015, Acta biomaterialia.

[4]  E. Itoi,et al.  Schwann cell transplantation for spinal cord injury repair: its significant therapeutic potential and prospectus , 2015, Reviews in the neurosciences.

[5]  D. Pearse,et al.  Permissive Schwann Cell Graft/Spinal Cord Interfaces for Axon Regeneration , 2015, Cell transplantation.

[6]  M. Weiss,et al.  Directed Migration of Embryonic Stem Cell-derived Neural Cells In An Applied Electric Field , 2014, Stem Cell Reviews and Reports.

[7]  Ying Yang,et al.  Alignment of multiple glial cell populations in 3D nanofiber scaffolds: toward the development of multicellular implantable scaffolds for repair of neural injury. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[8]  Juan Xiao,et al.  A Prospective Randomized Double-Blind Clinical Trial Using a Combination of Olfactory Ensheathing Cells and Schwann Cells for the Treatment of Chronic Complete Spinal Cord Injuries , 2014, Cell transplantation.

[9]  J. Guest,et al.  Clinical translation of autologous Schwann cell transplantation for the treatment of spinal cord injury , 2013, Current opinion in organ transplantation.

[10]  E. Biazar,et al.  Chitosan–Cross-Linked Nanofibrous PHBV Nerve Guide for Rat Sciatic Nerve Regeneration Across a Defect Bridge , 2013, ASAIO journal.

[11]  B. Zuo,et al.  Electrospun silk fibroin nanofibers in different diameters support neurite outgrowth and promote astrocyte migration. , 2013, Journal of biomedical materials research. Part A.

[12]  M. Soleimani,et al.  Safety and possible outcome assessment of autologous Schwann cell and bone marrow mesenchymal stromal cell co-transplantation for treatment of patients with chronic spinal cord injury. , 2013, Cytotherapy.

[13]  J. Burdick,et al.  Fiber alignment directs cell motility over chemotactic gradients. , 2013, Biotechnology and bioengineering.

[14]  X. Wen,et al.  A Novel Growth-Promoting Pathway Formed by GDNF-Overexpressing Schwann Cells Promotes Propriospinal Axonal Regeneration, Synapse Formation, and Partial Recovery of Function after Spinal Cord Injury , 2013, The Journal of Neuroscience.

[15]  Yonggang Huang,et al.  High performance piezoelectric devices based on aligned arrays of nanofibers of poly(vinylidenefluoride-co-trifluoroethylene) , 2013, Nature Communications.

[16]  D. Ying,et al.  Piezoelectric PU/PVDF electrospun scaffolds for wound healing applications. , 2012, Colloids and surfaces. B, Biointerfaces.

[17]  T. Arinzeh,et al.  The influence of piezoelectric scaffolds on neural differentiation of human neural stem/progenitor cells. , 2012, Tissue engineering. Part A.

[18]  W. Świȩszkowski,et al.  Electrospun bio-composite P(LLA-CL)/collagen I/collagen III scaffolds for nerve tissue engineering. , 2012, Journal of biomedical materials research. Part B, Applied biomaterials.

[19]  P. Tresco,et al.  The assessment of adeno‐associated vectors as potential intrinsic treatments for brainstem axon regeneration , 2012, The journal of gene medicine.

[20]  Xiaohong Kong,et al.  Transplantation of Autologous Activated Schwann Cells in the Treatment of Spinal Cord Injury: Six Cases, more than Five Years of Follow-up , 2012, Cell transplantation.

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

[22]  M. Yekaninejad,et al.  Safety of intramedullary Schwann cell transplantation for postrehabilitation spinal cord injuries: 2-year follow-up of 33 cases. , 2011, Journal of neurosurgery. Spine.

[23]  R. Puzis,et al.  Preparation of spinal cord injured tissue for light and electron microscopy including preparation for immunostaining , 2011 .

[24]  K. Cheung,et al.  Neural Repair , 2011 .

[25]  J. Mcdonald,et al.  Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers. , 2011, Biomaterials.

[26]  M. Fehlings,et al.  A systematic review of cellular transplantation therapies for spinal cord injury. , 2011, Journal of neurotrauma.

[27]  Xiao-Ming Xu,et al.  GDNF modifies reactive astrogliosis allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury , 2011, Experimental Neurology.

[28]  Li Yao,et al.  Electric field-guided neuron migration: a novel approach in neurogenesis. , 2011, Tissue engineering. Part B, Reviews.

[29]  Y. Liu,et al.  Guidance of neurite outgrowth on aligned electrospun polypyrrole/poly(styrene-beta-isobutylene-beta-styrene) fiber platforms. , 2010, Journal of biomedical materials research. Part A.

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

[31]  Casey K. Chan,et al.  Synergistic effects of electrospun PLLA fiber dimension and pattern on neonatal mouse cerebellum C17.2 stem cells. , 2010, Acta biomaterialia.

[32]  S. Heilshorn,et al.  Biomaterial design strategies for the treatment of spinal cord injuries. , 2010, Journal of neurotrauma.

[33]  Jae Young Lee,et al.  Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. , 2009, Biomaterials.

[34]  Kenneth M. Yamada,et al.  Random versus directionally persistent cell migration , 2009, Nature Reviews Molecular Cell Biology.

[35]  M. Bunge,et al.  Combinatorial strategies with Schwann cell transplantation to improve repair of the injured spinal cord , 2009, Neuroscience Letters.

[36]  V. Rahimi-Movaghar,et al.  Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: An interim report on safety considerations and possible outcomes , 2008, Neuroscience Letters.

[37]  L. Yao,et al.  Small applied electric fields guide migration of hippocampal neurons , 2008, Journal of cellular physiology.

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

[39]  S. Davies,et al.  Astrocytes Derived from Glial-restricted Precursors Promote Spinal Cord Repair , 2005 .

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

[41]  P. Tresco,et al.  Basic fibroblast growth factor promotes neuronal survival but not behavioral recovery in the transected and Schwann cell implanted rat thoracic spinal cord. , 2004, Journal of neurotrauma.

[42]  Jerry Silver,et al.  Regeneration beyond the glial scar , 2004, Nature Reviews Neuroscience.

[43]  S. Ramakrishna,et al.  Characterization of neural stem cells on electrospun poly(L-lactic acid) nanofibrous scaffold , 2004, Journal of biomaterials science. Polymer edition.

[44]  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.

[45]  M. Oudega,et al.  Schwann Cell But Not Olfactory Ensheathing Glia Transplants Improve Hindlimb Locomotor Performance in the Moderately Contused Adult Rat Thoracic Spinal Cord , 2002, The Journal of Neuroscience.

[46]  J. Fawcett,et al.  The glial scar and central nervous system repair , 1999, Brain Research Bulletin.

[47]  R. Cailliet,et al.  A review of biomechanics of the central nervous system--Part III: spinal cord stresses from postural loads and their neurologic effects. , 1999, Journal of manipulative and physiological therapeutics.

[48]  R. Cailliet,et al.  A review of biomechanics of the central nervous system--part II: spinal cord strains from postural loads. , 1999, Journal of manipulative and physiological therapeutics.

[49]  R. Cailliet,et al.  A review of biomechanics of the central nervous system--Part I: spinal canal deformations resulting from changes in posture. , 1999, Journal of manipulative and physiological therapeutics.

[50]  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.

[51]  M. Schwab,et al.  Degeneration and regeneration of axons in the lesioned spinal cord. , 1996, Physiological reviews.

[52]  P. Aebischer,et al.  A Combination of BDNF and NT-3 Promotes Supraspinal Axonal Regeneration into Schwann Cell Grafts in Adult Rat Thoracic Spinal Cord , 1995, Experimental Neurology.

[53]  N. Kleitman,et al.  Axonal regeneration into Schwann cell‐seeded guidance channels grafted into transected adult rat spinal cord , 1995, The Journal of comparative neurology.

[54]  Richard B. Dickinson,et al.  Biased cell migration of fibroblasts exhibiting contact guidance in oriented collagen gels , 1994, Annals of Biomedical Engineering.

[55]  M. Tabaton,et al.  GFAP expression of human Schwann cells in tissue culture , 1992, Brain Research.

[56]  R F Valentini,et al.  Improved nerve regeneration through piezoelectric vinylidenefluoride-trifluoroethylene copolymer guidance channels. , 1991, Biomaterials.

[57]  Paolo Dario,et al.  Piezoelectric guidance channels enhance regeneration in the mouse sciatic nerve after axotomy , 1987, Brain Research.

[58]  P. Dario,et al.  Piezoelectric nerve guidance channels enhance peripheral nerve regeneration. , 1987, ASAIO transactions.

[59]  A. Björklund,et al.  Dopamine‐containing neurons in the spinal cord: Anatomy and some functional aspects , 1983, Annals of neurology.

[60]  L. Davis Treatment of spinal cord injuries. , 1954, A.M.A. archives of surgery.

[61]  M. Bunge,et al.  Lentiviral vector-mediated transduction of neural progenitor cells before implantation into injured spinal cord and brain to detect their migration, deliver neurotrophic factors and repair tissue. , 2005, Restorative neurology and neuroscience.

[62]  L. Naldini,et al.  HIV-based vectors. Preparation and use. , 2002, Methods in molecular medicine.

[63]  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.

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