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Sci Adv. 2016 Apr 1;2(4):e1500887. doi: 10.1126/sciadv.1500887. eCollection 2016 Apr.

Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model.

Author information

1
Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
2
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.
3
Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
4
Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
5
Department of Regenerative Medicine, Plastic and Reconstructive Surgery, Kitasato University of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
6
Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi 980-8575, Japan.
7
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.

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.

KEYWORDS:

3D integumentary organ system; CDB method; Regenerative medicine; embryoid body; hair follicles; iPS cells; organ regeneration

PMID:
27051874
PMCID:
PMC4820374
DOI:
10.1126/sciadv.1500887
[Indexed for MEDLINE]
Free PMC Article

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