In vitro skin models to study epithelial regeneration from the hair follicle
Open accessAbstract
The development of dermal equivalents (DEs) for the treatment of burns has contributed toward efficient wound closure. A collagen-glycosaminoglycan DE (C-GAG) grafted with hair follicles converted a full-thickness wound to partial-thickness resulting in complete wound closure and restored hair. In this study we compared the ability of both intact pilosebaceous units (PSU) or truncated hair follicles (THF) to regenerate a multilayered epidermis in vitro when implanted into de-epidermalized dermis (DED) or C-GAG with the epidermis generated in vivo using C-CAG. Keratinocytes explanted from the outer root sheath of PSU and THF in both DED and C-GAG but only formed a multilayered epidermis with PSU in DED. PSU were more effective at forming multilayered epidermis in DED than THF. Both DED and C-GAG skin expressed proliferation (PCNA), differentiation (K1, K10), hyperproliferation (K6, K16), basal (K14), putative stem cell (p63), extracellular matrix protein (Collagen IV), mesenchymal (vimentin) and adherens junction (β-catenin) markers. These data suggest DEs supported initial maintenance of the implanted hair follicles, in particular PSU, and provide an excellent model with which to investigate the regulation of hair follicle progenitor epithelial cells during epidermal regeneration. Although neither PSU nor THF formed multilayered epidermis in C-CAG in vitro, hair follicles implanted into engrafted C-GAG on a burns patient resulted in epithelial regeneration and expression of proliferation and differentiation markers in a similar manner to that seen in vitro. However, the failure of C-GAG to support epidermal regeneration in vitro suggests in vivo factors are essential for full epidermal regeneration using C-GAG.
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The wounding keratins KRT6/KRT16 were expressed in the grafted region on days 16 and 37 in HSEs transplanted onto humans, with their expression disappearing a year after transplantation.
“the wounding keratins KRT6/KRT16 were expressed in the grafted region on days 16 and 37 in HSEs transplanted onto humans, with their expression disappearing a year after transplantation.68”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [68]
The Results section (‘Hyperproliferation and differentiation profile of skin equivalents and neo-epidermis in vivo’; page unavailable) reports K6 and K16 staining in the neo-epithelium at days 16 and 37, with patterns resembling control scalp skin at one year. But the Materials and methods section (‘Micrografting hair follicles into the engrafted C-GAG’; page unavailable) describes hair follicles micrografted into a scaffold engrafted on a burn patient, not HSEs transplanted onto humans. The paper also does not say K6/K16 expression disappeared entirely: control scalp skin retained expression in hair-follicle structures. (LLM, conf=0.88)
Experimental — accuracy not yet measuredKRT14 was expressed in all layers of the epidermis until a year post grafting, where it resumed normal BAS layer expression.
“KRT14 was expressed in all layers of the epidermis until a year post grafting, where it resumed normal BAS layer expression”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [68]
The Results section reports that K14 staining extended throughout the suprabasal layers at days 16 and 37 post-micrografting and resembled control scalp skin at one year. It does not establish that this pattern persisted throughout the intervening year. It also describes normal control-skin expression in the basal layer and one or two suprabasal layers, not the basal layer alone. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe tissue did not reach homeostasis until a year post grafting.
“suggesting that the tissue did not reach homeostasis until a year post grafting.68”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [68]
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- Authors
- Ojeh, N., Akgül, B., Tomic-Canic, M., Philpott, M., & Navsaria, H.
- Affiliations
- Queen Mary University of London (GB)
- Corresponding author
- Ojeh, Nkemcho
- ORCID
- Ojeh, Nkemcho
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-03-28
- Volume
- 12
- Issue
- 3
- Pages
- e0174389
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5370106
- OpenAlex
- W2600718354
- Cited by
- 23
- References
- 50
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 2 · 2020: 4 · 2019: 3 · 2018: 5 · 2016: 1
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- dermal equivalent, hair follicle, epidermal regeneration, pilosebaceous unit, keratinocytes, outer root sheath, burn wound closure, keratinocyte differentiation markers, β-catenin, p63, wound healing
- MeSH terms
- Epidermal Cells, Cells, Cultured, Epidermis, Humans, Regeneration, Keratinocytes, Skin, Artificial, Hair Follicle, Cell Proliferation
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