title: GDNF Schwann cells in hydrogel scaffolds promote regional axon regeneration, remyelination and functional improvement after spinal cord transection in rats.
abstract: Positively-charged oligo[poly(ethylene glycol)fumarate] (OPF+) is a biodegradable hydrogel used for spinal cord injury repair. We compared scaffolds containing primary Schwann cells (SCs) to scaffolds delivering SCs genetically modified to secrete high concentrations of glial cell-derived neurotrophic factor (GDNF). Multichannel OPF+scaffolds loaded with SCs or GDNF-SCs were implanted into transected rat spinal cords for 4 weeks. GDNF-SCs promoted regeneration of more axons into OPF+scaffolds (2773.0 ± 396.0) than primary SC OPF+scaffolds (1666.0 ± 352.2) (p = 0.0491). This increase was most significant in central and ventral-midline channels of the scaffold. Axonal remyelination was quantitated by stereologic analysis. Increased myelination of regenerating axons was observed in the GDNF-SC group. Myelinating cell and axon complexes were formed by host SCs and not by implanted cells or host oligodendrocytes. Fast Blue retrograde tracing studies determined the rostral-caudal directionality of axonal growth. The number of neurons that projected axons rostrally through the GDNF-SC scaffolds was higher (7929 ± 1670) than in animals with SC OPF+scaffolds (1069 ± 241.5) (p < 0.0001). The majority of ascending axons were derived from neurons located more than 15 mm from the scaffold-cord interface, and were identified to be lumbosacral intraspinal motor neurons. Transected animals with GDNF-SC OPF+scaffolds partially recovered locomotor function at weeks 3 and 4 following surgery. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Bingkun K
authors.initials: BK
authors.lastname: Chen
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Nicolas N
authors.initials: NN
authors.lastname: Madigan
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hakim
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.affiliation: Department of Medicine, Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway.
authors.forename: Siobhan S
authors.initials: SS
authors.lastname: McMahon
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Anthony J
authors.identifier: 0000-0003-3481-0274
authors.initials: AJ
authors.lastname: Windebank
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D005650:Fumarates / Q000737:chemistry; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D000074586:Remyelination / Q000187:drug effects*; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D005650:Fumarates; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020100:Hydrogels; C508734:poly(ethylene glycol fumarate); D011092:Polyethylene Glycols
keywords: Schwann cells; glial-derived neurotrophic factor; hydrogel; oligo[poly(ethylene glycol)fumarate]; scaffolds; spinal cord injury