title: Multifunctional, multichannel bridges that deliver neurotrophin encoding lentivirus for regeneration following spinal cord injury.
abstract: Therapeutic strategies following spinal cord injury must address the multiple barriers that limit regeneration. Multiple channel bridges have been developed that stabilize the injury following implantation and provide physical guidance for regenerating axons. These bridges have now been employed as a vehicle for localized delivery of lentivirus. Implantation of lentivirus loaded multiple channel bridges produced transgene expression that persisted for at least 4 weeks. Expression was maximal at the implant at the earliest time point, and decreased with increasing time of implantation, as well as rostral and caudal to the bridge. Immunohistochemical staining indicated transduction of macrophages, Schwann cells, fibroblasts, and astrocytes within the bridge and adjacent tissue. Subsequently, the delivery of lentivirus encoding the neurotrophic factors NT-3 or BDNF significantly increased the extent of axonal growth into the bridge relative to empty scaffolds. In addition to promoting axon growth, the induced expression of neurotrophic factors led to myelination of axons within the channels of the bridge, where the number of myelinated axons was significantly enhanced relative to control. Combining gene delivery with biomaterials to provide physical guidance and create a permissive environment can provide a platform to enhance axonal growth and promote regeneration.
authors: Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208-3120, USA.
authors: Hannah M
authors: HM
authors: Tuinstra
authors: Misael O
authors: MO
authors: Aviles
authors: Seungjin
authors: S
authors: Shin
authors: Samantha J
authors: SJ
authors: Holland
authors: Marina L
authors: ML
authors: Zelivyanskaya
authors: Alan G
authors: AG
authors: Fast
authors: Sarah Y
authors: SY
authors: Ko
authors: Daniel J
authors: DJ
authors: Margul
authors: Anne K
authors: AK
authors: Bartels
authors: Ryan M
authors: RM
authors: Boehler
authors: Brian J
authors: BJ
authors: Cummings
authors: Aileen J
authors: AJ
authors: Anderson
authors: Lonnie D
authors: LD
authors: Shea
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000494:pharmacology*; D020933:Neurotrophin 3 / Q000494:pharmacology; D019919:Prosthesis Implantation; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D058630:Spinal Cord Regeneration / Q000187:drug effects*; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3