title: Trophic Effects of Dental Pulp Stem Cells on Schwann Cells in Peripheral Nerve Regeneration.
abstract: Recently, mesenchymal stem cells have demonstrated a potential for neurotrophy and neurodifferentiation. We have recently isolated mobilized dental pulp stem cells (MDPSCs) using granulocyte-colony stimulating factor (G-CSF) gradient, which has high neurotrophic/angiogenic potential. The aim of this study is to investigate the effects of MDPSC transplantation on peripheral nerve regeneration. Effects of MDPSC transplantation were examined in a rat sciatic nerve defect model and compared with autografts and control conduits containing collagen scaffold. Effects of conditioned medium of MDPSCs were also evaluated in vitro. Transplantation of MDPSCs in the defect demonstrated regeneration of myelinated fibers, whose axons were significantly higher in density compared with those in autografts and control conduits only. Enhanced revascularization was also observed in the MDPSC transplants. The MDPSCs did not directly differentiate into Schwann cell phenotype; localization of these cells near Schwann cells induced several neurotrophic factors. Immunofluorescence labeling demonstrated reduced apoptosis and increased proliferation in resident Schwann cells in the MDPSC transplant compared with control conduits. These trophic effects of MDPSCs on proliferation, migration, and antiapoptosis in Schwann cells were further elucidated in vitro. The results demonstrate that MDPSCs promote axon regeneration through trophic functions, acting on Schwann cells, and promoting angiogenesis.
authors.affiliation: Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Morioka, Obu, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Osako
authors.forename: Masataka
authors.initials: M
authors.lastname: Ito
authors.forename: Masashi
authors.initials: M
authors.lastname: Murakami
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horibe
authors.forename: Koichiro
authors.initials: K
authors.lastname: Iohara
authors.forename: Norio
authors.initials: N
authors.lastname: Takeuchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okui
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kurita
authors.forename: Misako
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000166:cytology*; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned