title: Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury.
abstract: Schwann cell (SC) implantation after spinal cord injury (SCI) promotes axonal regeneration, remyelination repair, and functional recovery. Reparative efficacy, however, may be limited because of the inability of SCs to migrate outward from the lesion-implant site. Altering SC cell surface properties by overexpressing polysialic acid (PSA) has been shown to promote SC migration. In this study, a SCI contusion model was used to evaluate the migration, supraspinal axon growth support, and functional recovery associated with polysialyltransferase (PST)-overexpressing SCs [PST-green fluorescent protein (GFP) SCs] or controls (GFP SCs). Compared with GFP SCs, which remained confined to the injection site at the injury center, PST-GFP SCs migrated across the lesion:host cord interface for distances of up to 4.4 mm within adjacent host tissue. In addition, with PST-GFP SCs, there was extensive serotonergic and corticospinal axon in-growth within the implants that was limited in the GFP SC controls. The enhanced migration of PST-GFP SCs was accompanied by significant growth of these axons caudal to lesion. Animals receiving PST-GFP SCs exhibited improved functional outcome, both in the open-field and on the gridwalk test, beyond the modest improvements provided by GFP SC controls. This study for the first time demonstrates that a lack of migration by SCs may hinder their reparative benefits and that cell surface overexpression of PSA enhances the ability of implanted SCs to associate with and support the growth of corticospinal axons. These results provide further promise that PSA-modified SCs will be a potent reparative approach for SCI. © 2012 Wiley Periodicals, Inc.
authors.affiliation: Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Ghosh
authors.forename: Luis M
authors.initials: LM
authors.lastname: Tuesta
authors.forename: Rocio
authors.initials: R
authors.lastname: Puentes
authors.forename: Samik
authors.initials: S
authors.lastname: Patel
authors.forename: Kiara
authors.initials: K
authors.lastname: Melendez
authors.forename: Abderrahman
authors.initials: A
authors.lastname: El Maarouf
authors.forename: Urs
authors.initials: U
authors.lastname: Rutishauser
authors.forename: Damien Daniel
authors.initials: DD
authors.lastname: Pearse
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001710:Biotin / Q000031:analogs & derivatives; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects*; D003911:Dextrans; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016014:Linear Models; D008164:Luminescent Proteins / Q000235:genetics; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology / Q000637:transplantation; D012584:Sciatic Nerve / Q000166:cytology; D012701:Serotonin / Q000378:metabolism; D012794:Sialic Acids / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D003911:Dextrans; D008164:Luminescent Proteins; D012794:Sialic Acids; C076397:biotinylated dextran amine; C485184:enhanced green fluorescent protein; C021319:polysialic acid; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; D012701:Serotonin; D001710:Biotin