title: Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation.
abstract: Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2-8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.
authors.affiliation: Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan; Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Saito
authors.affiliation: Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan; Department of Physiological Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tamaki
authors.affiliation: Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan; Department of Orthopedics, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Hirata
authors.affiliation: Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan; Department of Orthopedics, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan; Department of General Thorathic Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Kenei
authors.initials: K
authors.lastname: Nakazato
authors.affiliation: Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan; Department of Urology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nakajima
authors.affiliation: Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan; Department of Gastroenterological Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Kazuno
authors.affiliation: Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sakai
authors.affiliation: Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iida
authors.affiliation: Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okami
mesh_terms: D000818:Animals; D005154:Facial Nerve / Q000098:blood supply / Q000502:physiology / Q000601:surgery*; D005260:Female; D008297:Male; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000166:cytology*; D051381:Rats; D020127:Recovery of Function; D033581:Stem Cell Transplantation