title: Preferential Enhancement of Sensory and Motor Axon Regeneration by Combining Extracellular Matrix Components with Neurotrophic Factors.
abstract: After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively. For in vivo studies, the rat sciatic nerve was transected and repaired with a silicone tube filled with a collagen and laminin matrix with NGF/NT3 encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres (MP) (LM + MP.NGF/NT3), or a collagen and fibronectin matrix with BDNF in PLGA MPs (FN + MP.BDNF). Retrograde labeling and functional tests showed that LM + MP.NGF/NT3 increased the number of regenerated sensory neurons and improved sensory functional recovery, whereas FN + MP.BDNF preferentially increased regenerated motoneurons and enhanced motor functional recovery. Therefore, combination of ECM molecules with NTFs may be a good approach to selectively enhance motor and sensory axons regeneration and promote appropriate target reinnervation.
authors.affiliation: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. dani.santos.1988@hotmail.com.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), E-08193 Bellaterra, Spain. dani.santos.1988@hotmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Santos
authors.affiliation: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. francisco.gzlez@gmail.com.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), E-08193 Bellaterra, Spain. francisco.gzlez@gmail.com.
authors.forename: Francisco
authors.initials: F
authors.lastname: González-Pérez
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy. g.giudetti@sssup.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Giudetti
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy. micera@sssup.it.|Bertarelli Foundation Chair in Translational NeuroEngineering, Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Interfaculty Institute of Bioengineering, School of Engineering, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. micera@sssup.it.
authors.forename: Silvestro
authors.initials: S
authors.lastname: Micera
authors.affiliation: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. esther.udina@uab.cat.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), E-08193 Bellaterra, Spain. esther.udina@uab.cat.
authors.forename: Esther
authors.initials: E
authors.lastname: Udina
authors.affiliation: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. jaume.delvalle@uab.cat.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), E-08193 Bellaterra, Spain. jaume.delvalle@uab.cat.
authors.forename: Jaume
authors.initials: J
authors.lastname: Del Valle
authors.affiliation: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. xavier.navarro@uab.cat.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), E-08193 Bellaterra, Spain. xavier.navarro@uab.cat.
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008863:Microspheres; D009046:Motor Neurons / Q000502:physiology*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000187:drug effects*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins; D009414:Nerve Growth Factors
keywords: BDNF; NGF; NT3; extracellular matrix; motor axons; nerve regeneration; neurotrophic factors; reinnervation; sensory axons