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Cited by 307Hair Growth and DisordersTissue Engineering and Regenerative Medicine3D Printing in Biomedical Research

Tissue engineering of human hair follicles using a biomimetic developmental approach

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Abaci, Hasan Erbil, Coffman, Abigail, Doucet, Yanne, Chen, James, Jacków, Joanna, Wang, Etienne, Guo, Zongyou, Shin, Jung U. +2 more·2018·Nature Communications
DOI 10.1038/s41467-018-07579-yPMC PMC6294003
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Abstract

Human skin constructs (HSCs) have the potential to provide an effective therapy for patients with significant skin injuries and to enable human-relevant drug screening for skin diseases; however, the incorporation of engineered skin appendages, such as hair follicles (HFs), into HSCs remains a major challenge. Here, we demonstrate a biomimetic approach for generation of human HFs within HSCs by recapitulating the physiological 3D organization of cells in the HF microenvironment using 3D-printed molds. Overexpression of Lef-1 in dermal papilla cells (DPC) restores the intact DPC transcriptional signature and significantly enhances the efficiency of HF differentiation in HSCs. Furthermore, vascularization of hair-bearing HSCs prior to engraftment allows for efficient human hair growth in immunodeficient mice. The ability to regenerate an entire HF from cultured human cells will have a transformative impact on the medical management of different types of alopecia, as well as chronic wounds, which represent major unmet medical needs.

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  • 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 [22]

    The Introduction (page not available) says currently available human skin constructs have poor long-term viability and lack appendages such as hair follicles. The Results report no sebocyte differentiation in the authors’ constructs and describe culturing them for three weeks, but do not establish that human skin equivalents generally have a 2–3-week culture limit. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • aHSEs can integrate additional cell types including endothelial cells, melanocytes, neuronal cells, lymphatic cells, immune cells, adipocytes, pluripotent stem cells, and skin appendages.

    “These include endothelial cells to vascularize the dermis [46] and melanocytes to introduce pigmentation [47]. Furthermore, neuronal cells [48,49], lymphatic cells [50], immune cells (e.g. dermal dendritic cells [51], monocytes [52], T cells [53], and macrophages [54]), adipocytes and adipose tissue [49,55,56], pluripotent stem cells [22,36,57], and skin appendages such as hair follicles or sweat”

    From Diversity of human skin three-dimensional organotypic cultures (2024) · cites this paper as [58]

  • 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 [4]

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References 43 · Cited by 307

Research works printed but not linked: 37

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Authors
Abaci, H. E., Coffman, A., Doucet, Y., Chen, J., Jacków, J., Wang, E., Guo, Z., Shin, J. U., Jahoda, C. A., & Christiano, A. M.
Affiliations
  • Columbia University Irving Medical Center (US)
  • Durham University (GB)
Corresponding author
Christiano, Angela M.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-12-13
Volume
9
Issue
1
Pages
5301-5301
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-07579-y
PMC
PMC6294003
OpenAlex
W2904060869
Cited by
307
References
43
Citations by year
2026: 35 · 2025: 39 · 2024: 42 · 2023: 49 · 2022: 38 · 2021: 50 · 2020: 39 · 2019: 14
FWCI
34.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Durham Research Online (Durham University) (acceptedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Durham Research Online (Durham University) (submittedVersion, cc-by)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • New York State Stem Cell Science
  • Danish Cancer Society Research Center
  • National Institutes of Health (UL1TR001873)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR069632, K01AR072131)
  • National Institute of Biomedical Imaging and Bioengineering (UH2EB017103)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
hair follicle regeneration, dermal papilla cells, LEF1, 3D-printed molds, biomimetic microenvironment, hair follicle differentiation, vascularization, hair loss, chronic wounds, skin appendages, drug screening
MeSH terms
Alopecia, Animals, Cell Differentiation, Cells, Cultured, Humans, Male, Mice, Nude, Transplantation, Heterologous, Hair Follicle, Dermis, Tissue Engineering, Biomimetics, Mice, Lymphoid Enhancer-Binding Factor 1, Human Umbilical Vein Endothelial Cells

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