title: Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model.
abstract: The integumentary organ system is a complex system that plays important roles in waterproofing, cushioning, protecting deeper tissues, excreting waste, and thermoregulation. We developed a novel in vivo transplantation model designated as a clustering-dependent embryoid body transplantation method and generated a bioengineered three-dimensional (3D) integumentary organ system, including appendage organs such as hair follicles and sebaceous glands, from induced pluripotent stem cells. This bioengineered 3D integumentary organ system was fully functional following transplantation into nude mice and could be properly connected to surrounding host tissues, such as the epidermis, arrector pili muscles, and nerve fibers, without tumorigenesis. The bioengineered hair follicles in the 3D integumentary organ system also showed proper hair eruption and hair cycles, including the rearrangement of follicular stem cells and their niches. Potential applications of the 3D integumentary organ system include an in vitro assay system, an animal model alternative, and a bioengineered organ replacement therapy.
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Takagi
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Ishimaru
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Sugawara
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.; Organ Technologies Inc., Minato-ku, Tokyo 105-0001, Japan.; Department of Regenerative Medicine, Plastic and Reconstructive Surgery, Kitasato University of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Koh-Ei
authors.initials: KE
authors.lastname: Toyoshima
authors.affiliation: Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ishida
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.; Organ Technologies Inc., Minato-ku, Tokyo 105-0001, Japan.; Department of Regenerative Medicine, Plastic and Reconstructive Surgery, Kitasato University of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Miho
authors.identifier: 0000-0002-9576-3478
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sakakibara
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Asakawa
authors.affiliation: Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Kashiwakura
authors.affiliation: Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Minamide
authors.affiliation: Department of Regenerative Medicine, Plastic and Reconstructive Surgery, Kitasato University of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Regenerative Medicine, Plastic and Reconstructive Surgery, Kitasato University of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Toshihiro
authors.identifier: 0000-0002-8963-7512
authors.initials: T
authors.lastname: Yoshitake
authors.affiliation: Department of Regenerative Medicine, Plastic and Reconstructive Surgery, Kitasato University of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takeda
authors.affiliation: Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Egusa
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.; Organ Technologies Inc., Minato-ku, Tokyo 105-0001, Japan.; Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D057005:Bioengineering; D018859:Hair Follicle / Q000637:transplantation*; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D034582:Integumentary System / Q000254:growth & development; D051379:Mice; D016377:Organ Transplantation / Q000379:methods; D012627:Sebaceous Glands / Q000637:transplantation; D012867:Skin / Q000254:growth & development
keywords: 3D integumentary organ system; CDB method; Regenerative medicine; embryoid body; hair follicles; iPS cells; organ regeneration