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Cited by 132Pluripotent Stem Cells Researchmelanin and skin pigmentationHair Growth and Disorders

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells

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Gledhill, Karl, Guo, Zongyou, Umegaki-Arao, Noriko, Higgins, Claire A., Itoh, Munenari, Christiano, Angela M.·2015·PLOS ONE
DOI 10.1371/journal.pone.0136713PMC PMC4550351
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Abstract

The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

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  • Reconstruction of appendage-bearing skin in cultures and in bioengineered grafts remains an unmet biomedical challenge.

    “Reconstruction of appendage-bearing skin in cultures and in bioengineered grafts remains an unmet biomedical challenge3–9.”

    From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [5]

    The Introduction (page unavailable) says current cultured human 3D skin equivalents lack appendages and that adding complex structures such as appendages remains a hurdle. The paper does not address whether reconstructing appendage-bearing skin in bioengineered grafts remains a challenge. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Human skin equivalents have notable drawbacks, such as a lack of crucial skin tissue structures (e.g., hair follicles and sebaceous glands) and limited culture durations (e.g., 2-3 weeks).

    “However, human skin equivalents have notable drawbacks, such as a lack of crucial skin tissue structures (e.g., hair follicles and sebaceous glands) and limited culture durations (e.g., 2–3 weeks)”

    From Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells (2022) · cites this paper as [21]

    The Introduction says human skin equivalents lack appendages, supporting the point about missing structures such as hair follicles and sebaceous glands. The Methods describe harvesting this study’s constructs 14 days after raising them to the air–liquid interface, but do not establish a general culture-duration limit of 2–3 weeks. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In vitro skin derivation strategies have focused on generating keratinocytes and fibroblasts from pluripotent stem cells in separate cultures first, then combining the two cell types to form a skin-like bilayer.

    “To date, in vitro skin derivation strategies have focused on generating keratinocytes and fibroblasts from PSCs in separate cultures first, then combining the two types of cells to form a skin-like bilayer (Gledhill et al., 2015; Itoh et al., 2013; Oh et al., 2013; Sun et al., 2014).”

    From Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids (2018) · cites this paper as Gledhill et al., 2015

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References 40 · Cited by 132

Research works printed but not linked: 35

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Authors
Gledhill, K., Guo, Z., Umegaki-Arao, N., Higgins, C. A., Itoh, M., & Christiano, A. M.
Affiliations
Columbia University (US)
Corresponding author
Christiano, Angela M.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-08-26
Volume
10
Issue
8
Pages
e0136713
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0136713
PMC
PMC4550351
OpenAlex
W1954901000
Cited by
132
References
40
Citations by year
2026: 1 · 2025: 5 · 2024: 9 · 2023: 11 · 2022: 20 · 2021: 18 · 2020: 19 · 2019: 14 · 2018: 17 · 2017: 10 · 2016: 8
FWCI
5.07
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Columbia Academic Commons (Columbia University)
Funders
  • Stanford Diabetes Research Center
  • National Institutes of Health (U18TR000561)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
Keywords
3D skin equivalents, induced pluripotent stem cells, melanin transfer, melanocytes, epidermal melanocytes, skin pigmentation, iPSC-derived fibroblasts
MeSH terms
Epidermal Cells, Cell Differentiation, Cells, Cultured, Epidermis, Fibroblasts, Fluorescent Antibody Technique, Humans, Melanins, Melanocytes, RNA, Messenger, Skin, Biomarkers, Keratinocytes, Coculture Techniques, Cell Culture Techniques, Reverse Transcriptase Polymerase Chain Reaction, Induced Pluripotent Stem Cells, Real-Time Polymerase Chain Reaction

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