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Cited by 107Hair Growth and DisordersPluripotent Stem Cells ResearchTissue Engineering and Regenerative Medicine

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

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Takagi, Ryoji, Ishimaru, Junko, Sugawara, Ayaka, Toyoshima, Koh-ei, Ishida, Kentaro, Ogawa, Miho, Sakakibara, Kei, Asakawa, Kyosuke +8 more·2016·Science Advances
DOI 10.1126/sciadv.1500887PMC PMC4820374
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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.

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  • A system for generating integumentary tissues was described in which mouse embryonic stem cell aggregates were partially differentiated and then placed in the kidney capsule of athymic mice.

    “More recently, a system for generating integumentary tissues was described in which mouse embryonic stem cell aggregates were partially differentiated and then placed in the kidney capsule of athymic mice (Takagi et al., 2016).”

    From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Takagi et al., 2016

    The Results (In vivo induction of epithelial tissue) and Methods (iPS cell–derived EB transplantation and extraction) describe partially differentiated mouse iPS-cell aggregates transplanted beneath the kidney capsule to generate integumentary tissues. The citing sentence instead calls them embryonic stem-cell aggregates and describes the recipients as athymic mice; the transplantation Methods specify SCID mice. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Following transplantation, the aggregates preferentially differentiated into full-thickness skin layers in a cyst-like conformation and produced HFs.

    “Following transplantation, the aggregates preferentially differentiated into full-thickness skin layers in a cyst-like conformation and produced HFs.”

    From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Takagi et al., 2016

    The Results sections on CDB transplantation and the bioengineered integumentary organ system (page unavailable) describe cystic tissue containing epidermal, dermal and subdermal layers and hair follicles. They do not establish that the transplanted aggregates preferentially differentiated into skin: the paper also reports respiratory and gastrointestinal epithelia in the explants. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The mouse is a standard model for investigating skin development and disease in vivo.

    “The mouse is a standard model for investigating skin development and disease in vivo”

    From Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells (2022) · cites this paper as [16]

    The Methods section describes mouse skin samples and transplantation into mice, and the Results section uses natural mouse skin to assess a bioengineered skin system in vivo. This supports the use of mice to investigate skin development, but the paper does not establish that mice are a standard model for investigating skin disease. (LLM, conf=0.80)

    Experimental — accuracy not yet measured

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Authors
Takagi, R., Ishimaru, J., Sugawara, A., Toyoshima, K.-E., Ishida, K., Ogawa, M., Sakakibara, K., Asakawa, K., Kashiwakura, A., Oshima, M., Minamide, R., Sato, A., Yoshitake, T., Takeda, A., Egusa, H., & Tsuji, T.
Affiliations
  • Tokyo University of Science (JP)
  • Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
  • Research Institute for Science and Technology, Tokyo University of Science (JP)
  • RIKEN (JP)
  • Kitasato University (JP)
  • Tohoku University (JP)
Corresponding author
  • Takagi, Ryoji
  • Ishimaru, Junko
  • Sugawara, Ayaka
  • Tsuji, Takashi
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2016-04
Volume
2
Issue
4
Pages
e1500887-e1500887
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.1500887
PMC
PMC4820374
OpenAlex
W2333690258
Cited by
107
References
3
Citations by year
2026: 2 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 13 · 2021: 13 · 2020: 6 · 2019: 17 · 2018: 13 · 2017: 14 · 2016: 2
FWCI
22.36
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Grant-in-Aid for KIBAN (A) from the Ministry of Education, Culture, Sports and Technology (ID0EY2BK5543, 25242041)
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
induced pluripotent stem cells, hair follicle, sebaceous glands, nude mice, hair cycle, hair follicle stem cells, arrector pili muscle, nerve innervation, organ replacement therapy
MeSH terms
Animals, Sebaceous Glands, Skin, Organ Transplantation, Hair Follicle, Integumentary System, Mice, Bioengineering, Induced Pluripotent Stem Cells

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