title: Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury.
abstract: While neural stem/progenitor cells (NPCs) show promise for traumatic spinal cord injury (SCI), their efficacy in cervical SCI remains to be established. Moreover, their application to SCI is limited by the challenges posed by the lesion including the glial scar and the post-traumatic cavitation. Given this background, we sought to examine the synergistic effect of self-assembling peptide (SAP) molecules, designed to optimize the post-traumatic CNS microenvironment, and NSCs in a clinically-relevant model of contusive/compressive cervical SCI. We injected K2(QL)6K2 (QL6) SAPs into the lesion epicenter 14 days after bilateral clip compression-induced cervical SCI in rats, combined with simultaneous transplantation of neural stem/progenitor cells (NPCs) intraspinally adjacent to the lesion epicenter. The QL6 SAPs reduced the volume of cystic cavitation in the spinal cord lesion. Simultaneously engrafted NPCs preserved motor neurons and attenuated perilesional inflammation. The combination of QL6 and NPCs promoted forelimb neurobehavioral recovery and was associated with significant improvement in forelimb print area and stride length. In summary, we report for the first time histologic and functional benefits in a clinically-relevant model of cervical SCI through the synergistic effects of combined SAP and NPCs.
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada; Institutes of Medical Science, University of Toronto, University Health Network Toronto, ON M5S 1A8, Canada.
authors.forename: Jared T
authors.initials: JT
authors.lastname: Wilcox
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zweckberger
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada; Institutes of Medical Science, University of Toronto, University Health Network Toronto, ON M5S 1A8, Canada.
authors.forename: Spyridon K
authors.initials: SK
authors.lastname: Karadimas
authors.affiliation: Krembil Neuroscience Center, University Health Network, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada; Institutes of Medical Science, University of Toronto, University Health Network Toronto, ON M5S 1A8, Canada. Electronic address: Michael.Fehlings@uhn.ca.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002574:Cervical Vertebrae / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005552:Forelimb / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005684:Gait / Q000187:drug effects; D005911:Gliosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D010455:Peptides
keywords: Cervical cord injury; Functional recovery; Neural precursor cell; Self-assembling nanofiber; Tissue preservation