title: Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration.
abstract: Cell transplantation therapy has long been investigated as a therapeutic intervention for neurodegenerative disorders, including spinal cord injury, Parkinson's disease, and amyotrophic lateral sclerosis. Indeed, patients have high hopes for a cell-based therapy. However, there are numerous practical challenges for clinical translation. One major problem is that only very low numbers of donor cells survive and achieve functional integration into the host. Glial scar tissue in chronic neurodegenerative disorders strongly inhibits regeneration, and this inhibition must be overcome to accomplish successful cell transplantation. Intraneural cell transplantation is considered to be the best way to deliver cells to the host. We questioned this view with experiments in vivo on a rat glial scar model of the auditory system. Our results show that intraneural transplantation to the auditory nerve, preceded by chondroitinase ABC (ChABC)-treatment, is ineffective. There is no functional recovery, and almost all transplanted cells die within a few weeks. However, when donor cells are placed on the surface of a ChABC-treated gliotic auditory nerve, they autonomously migrate into it and recapitulate glia- and neuron-guided cell migration modes to repair the auditory pathway and recover auditory function. Surface transplantation may thus pave the way for improved functional integration of donor cells into host tissue, providing a less invasive approach to rescue clinically important neural tracts.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; tsekiya@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sekiya
authors.affiliation: Department of Biomedical Science, The University of Sheffield, Sheffield S10 2TN, United Kingdom;
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Holley
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
authors.forename: Kento
authors.initials: K
authors.lastname: Hashido
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ono
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shimomura
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
authors.forename: Rie T
authors.initials: RT
authors.lastname: Horie
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Hamaguchi
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
authors.forename: Tatsunori
authors.identifier: http://orcid.org/0000-0001-6669-7013
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage; D003056:Cochlear Nerve / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009416:Nerve Regeneration; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000628:therapy; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019765:Chondroitin ABC Lyase
keywords: astrocyte; auditory system; cell transplantation; glial scar; neurodegenerative diseases