title: Long-distance growth and connectivity of neural stem cells after severe spinal cord injury.
abstract: Neural stem cells (NSCs) expressing GFP were embedded into fibrin matrices containing growth factor cocktails and grafted to sites of severe spinal cord injury. Grafted cells differentiated into multiple cellular phenotypes, including neurons, which extended large numbers of axons over remarkable distances. Extending axons formed abundant synapses with host cells. Axonal growth was partially dependent on mammalian target of rapamycin (mTOR), but not Nogo signaling. Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery. Two human stem cell lines (566RSC and HUES7) embedded in growth-factor-containing fibrin exhibited similar growth, and 566RSC cells supported functional recovery. Thus, properties intrinsic to early-stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth, resulting in formation of new relay circuits that significantly improve function. These therapeutic properties extend across stem cell sources and species.
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Lu
authors.forename: Yaozhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Lori
authors.initials: L
authors.lastname: Graham
authors.forename: Karla
authors.initials: K
authors.lastname: McHale
authors.forename: Mingyong
authors.initials: M
authors.lastname: Gao
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: John
authors.initials: J
authors.lastname: Brock
authors.forename: Armin
authors.initials: A
authors.lastname: Blesch
authors.forename: Ephron S
authors.initials: ES
authors.lastname: Rosenzweig
authors.forename: Leif A
authors.initials: LA
authors.lastname: Havton
authors.forename: Binhai
authors.initials: B
authors.lastname: Zheng
authors.forename: James M
authors.initials: JM
authors.lastname: Conner
authors.forename: Martin
authors.initials: M
authors.lastname: Marsala
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002460:Cell Line; D005260:Female; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000628:therapy*; D058630:Spinal Cord Regeneration
chemical_list: D049452:Green Fluorescent Proteins