title: Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.
abstract: Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine , Nagoya, Japan .
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sugimura-Wakayama
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine , Nagoya, Japan .
authors.forename: Wataru
authors.initials: W
authors.lastname: Katagiri
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine , Nagoya, Japan .
authors.forename: Masashi
authors.initials: M
authors.lastname: Osugi
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine , Nagoya, Japan .
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kawai
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine , Nagoya, Japan .|2 Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University , Fukuoka, Japan .
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ogata
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine , Nagoya, Japan .
authors.forename: Kohei
authors.initials: K
authors.lastname: Sakaguchi
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine , Nagoya, Japan .
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hibi
mesh_terms: D000200:Action Potentials; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration; D055495:Neurogenesis; D059348:Peripheral Nerve Injuries / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology; D014094:Tooth, Deciduous / Q000166:cytology*
chemical_list: D009414:Nerve Growth Factors