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Cited by 6Hair Growth and DisordersPluripotent Stem Cells ResearchTissue Engineering and Regenerative Medicine

Hair Follicle Organoids Using Human iPSC-Derived Ectodermal Precursor Cells for Hair Regenerative Medicine

Open access
Kageyama, Tatsuto, Anakama, Riki, Hamano, Sayuri, Tu, Shan, Migita, Yuki, Asaba, Tomoki, Nanmo, Ayaka, Ishikawa, Kouyou +3 more·2026·ACS Biomaterials Science & Engineering
DOI 10.1021/acsbiomaterials.5c01780PMC PMC12976999
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Abstract

High Resolution Image Download MS PowerPoint Slide Organoids containing hair follicles can be regenerated in vitro using human induced pluripotent stem cells (hiPSCs) and potentially used as a tissue graft for hair regeneration. There are two main approaches to organoid formation: one is to form embryoid bodies from hiPSCs and induce differentiation into several organs and tissues, and the other is to induce tissue precursor epithelial and mesenchymal cells from hiPSCs and coculture them to generate organs and tissues via epithelial-mesenchymal interaction. Our ultimate aim is to differentiate hiPSCs into hair follicle epithelial and mesenchymal stem cells, and to subsequently purify and use them to generate hair follicle organoids (HFOs). We previously showed that murine embryonic skin-derived stem cells could be used to generate mouse HFOs with ∼100% efficiency. However, the key to inducing mouse HFOs is the supplementation of Matrigel at very low concentrations, and this mouse tumor-derived matrix cannot be applied in human treatment. In the current study, we found that collagen I provided a microenvironment for inducing HFOs that was equivalent to that induced by Matrigel. Furthermore, hiPSCs were differentiated into human ectodermal precursor cells and subsequently used to generate human/mouse chimeric HFOs with mouse embryonic mesenchymal cells. The human/mouse chimeric HFOs showed hair follicle sprouting both in vitro and in vivo . Although another approach to induce human mesenchymal layer cells from hiPSCs is necessary to generate fully human HFOs, this study demonstrates the potential of employing hiPSC-derived ectodermal precursor cells (hiPSC-EPCs) in HFO cultures in hair regenerative medicine.

AI snapshot

Written from the paper’s full text.

TL;DR

Collagen I can replace Matrigel for mouse hair follicle organoid (HFO) culture, and hiPSC-derived ectodermal precursor cells (hiPSC-EPCs) form human/mouse chimeric HFOs that sprout hair in vitro and regenerate hair shafts after transplantation. The study supports hiPSC-EPCs as a potential epithelial cell source for hair regenerative medicine, though fully human HFOs and safety assessments remain future work.

Key findings

  • Mouse collagen-based HFOs (cHFOs) showed significantly more hair follicle sprouting at collagen I concentrations of 24–240 μg/mL; 24 and 120 μg/mL were used for subsequent experiments, and generated mouse hair follicles elongated by ∼200 μm after 8 days.
  • In patch assays, mouse cHFOs and Matrigel-based HFOs produced significantly more hairs than HFGs without ECM, with no significant difference between cHFOs and mHFOs; cHFO transplantation yielded 4 hair follicles/10⁴ cells versus ∼1.3 hair follicles/10⁴ cells for conventional cell suspension transplantation.
  • hiPSCs differentiated into hiPSC-EPCs, with 83.5% KRT18-positive cells at day 11; human/mouse chimeric HFOs showed 13.6% hair generation efficiency (16/118 HFOs), whereas aggregates with only mouse mesenchymal cells showed 0/96.
  • Human/mouse chimeric cHFOs prepared with hiPSC-EPCs and mouse mesenchymal cells regenerated hair shafts in vivo, while controls using human fetal epithelial cells, mouse mesenchymal cells alone, or passaged human fetal epithelial cells did not.

Methods

  • Mouse embryonic skin-derived epithelial and mesenchymal layer cells were isolated from E18 dorsal skin and cultured in 96-well spheroid formation plates with collagen I (2.4–480 μg/mL tested; 24 or 120 μg/mL used) or 2% v/v Matrigel.
  • hiPSCs (201B7 line) were expanded feeder-free on Easy iMatrix511 and differentiated into hiPSC-EPCs using retinoic acid/BMP4 and keratinocyte serum-free medium; differentiation was assessed by RT-qPCR, immunostaining, and flow cytometry.
  • Human/mouse chimeric HFOs were prepared by mixing hiPSC-EPCs with mouse embryonic mesenchymal layer cells in collagen I or Matrigel, cultured for 6–10 days, and transplanted into nude or SCID hairless outbred mice via patch assays; hair shafts were counted after 3 weeks. Statistical analysis used Student’s t test or Tukey’s test with p < 0.05.

Limitations

  • The paper states that fully human HFOs require hiPSC-derived mesenchymal cells, which were not used here; the current system is human/mouse chimeric, and xenograft transplantation raises safety concerns for clinical application.
  • The paper states that detailed teratoma assessments were not conducted, and possible mouse epithelial cell contamination in the mesenchymal population may contribute to chimeric hair regeneration; chimeric HFO efficiency was low (13.6%) compared with mouse HFOs (∼100%).
  • The paper notes hiPSC limitations including epigenetic memory, high development costs, and time-consuming differentiation; evident from the text, the study lacks human clinical data and relies on immunodeficient mouse transplantation models.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1021/acsbiomaterials.5c01780

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 1 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Collagen I at concentrations between 24 and 240 μg/mL produced significantly more hair follicle sprouting in mouse HFOs than other tested concentrations.

    “Collagen I concentrations varying from 2.4 to 480 μg/mL were evaluated, and a significantly larger number of hair follicle sprouting was observed at doses between 24 and 240 μg/mL (Figure b).”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no significant difference in the number of hairs generated with mouse cHFOs between three and 6 days of culture before transplantation.

    “However, a significant difference in the number of hairs generated with the cHFOs between three and 6 days of culture before transplantation was not observed (Figures and S3).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Mouse cHFOs generated in vitro possessed typical hair follicle structures, including hair bulbs, hair shafts, dermal papillae, adipose and hair bulges.

    “A morphological analysis of mouse cHFOs revealed that hair follicles generated in vitro possessed typical hair follicle structures, including hair bulbs, hair shafts, dermal papillae, adipose and hair bulges (Figure c–l).”
    Quote in the paperSubstantial claim
  • Findingown data

    In the present study, cHFO transplantation regenerated 4 hair follicles per 10^4 cells.

    “In the present study (cHFO transplantation), 4 hair follicles/104 cells were regenerated by cHFO transplantation”
    Quote in the paperSubstantial claim
  • Findingown data

    At the lowest collagen I concentration (2.4 μg/mL), mouse HFO cells formed dumbbell-shaped structures with no hair follicle sprouting, similar to HFGs without ECM supplement.

    “At the lowest concentration (2.4 μg/mL), the cells formed dumbbell-shaped structures with no hair follicle sprouting, similar to HFGs under the condition without ECM supplement (Figure S2).”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 1
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 19

  • The quote only partly states this claim.

    Findingown data

    hiPSC-EPCs were used to generate human/mouse chimeric HFOs with mouse embryonic mesenchymal cells.

    “Furthermore, hiPSCs were differentiated into human ectodermal precursor cells and subsequently used to generate human/mouse chimeric HFOs with mouse embryonic mesenchymal cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    At collagen I concentrations >240 μg/mL, mouse HFO cells formed aggregates with core-shell structures but significantly fewer sprouts were observed.

    “At higher concentrations (>240 μg/mL), while cells formed aggregates with core–shell structures, significantly fewer sprouts were observed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Versican/Sox2-positive dermal papilla cells, CD34/KRT15-positive hair follicle stem cells, c-KIT/gp100-positive melanocyte and oil red O-positive adipocyte resided in regenerated hair follicles from mouse cHFOs, similar to native hair follicles.

    “Versican/Sox2-positive dermal papilla cells, CD34/KRT15-positive hair follicle stem cells, c-KIT/gp100-positive melanocyte and oil red O-positive adipocyte resided in these regenerated hair follicles (Figure e–l), similar to native hair follicles.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Restriction of cell migration in mouse HFOs was observed from collagen I concentrations >240 μg/mL, and was more significant from >360 μg/mL.

    “Restriction of cell migration was observed from >240 μg/mL, but it was more significant from >360 μg/mL.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The average hair follicle length and thickness was ∼200 and 100 μm, respectively.

    “The average hair follicle length and thickness was ∼200 and 100 μm, respectively (Figure S4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    cHFOs prepared from hiPSC-EPCs showed hair shaft generation, including black hair shafts.

    “cHFOs prepared from hiPSC-EPCs showed hair shaft generation”
    • Also stated in: § Transplantation of Human/Mouse Chimeric cHFOs Prepared with hiPSC-EPCs · plain
      “black hair shafts were regenerated in human/mouse chimeric cHFOs prepared with hiPSC-EPCs (cHFO (hiPSC-Epi/mMes)).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    During the culture period, the gene expression of the pluripotency markers OCT4 and SOX2 decreased, and that of the EPC marker KRT18 increased.

    “During the culture period, the gene expression of the pluripotency markers OCT4 and SOX2 decreased, and that of the EPC marker KRT18 increased (Figure d).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No hair regeneration was observed with human/mouse chimeric cHFOs prepared from human adult skin-derived epithelial layer cells, mouse embryonic mesenchymal layer cells, or aggregates composed solely of mouse embryonic mesenchymal layer cells.

    “no hair regeneration was observed with human/mouse chimeric cHFOs prepared from human adult skin-derived epithelial layer cells, mouse embryonic mesenchymal layer cells, or aggregates composed solely of mouse embryonic mesenchymal layer cells (Figure b,c).”
    • Also stated in: § Transplantation of Human/Mouse Chimeric cHFOs Prepared with hiPSC-EPCs · plain
      “In this study, hair follicles were not regenerated in mouse mesenchymal layer cells (spheroids (-/mMes)) (Figure b,c)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Human hair follicle organoids prepared by coculturing passaged human dermal papilla cells with human iPSC-derived epithelial cells initially formed single aggregates, which spontaneously generated hair-peg-like sprouts through epithelial-mesenchymal interactions, but further morphogenesis for mature hair follicles could not be observed.

    “These cells initially formed single aggregates, which spontaneously generated hair-peg-like sprouts through epithelial-mesenchymal interactions, but further morphogenesis for mature hair follicles could not observed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The hiPSCs formed typical stem cell colonies and expressed the undifferentiated hiPSC markers ALP, SSEA4, OCT-3/4, and TRA-1-60.

    “The hiPSCs formed typical stem cell colonies and expressed the undifferentiated hiPSC markers alkaline phosphatase (ALP), stage-specific embryonic antigen-4 (SSEA4), octamer binding transcription factor-3/4 (OCT-3/4), and TRA-1–60 (Figure b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    hiPSC-EPCs mixed with mouse embryonic skin-derived mesenchymal layer cells formed spherical aggregates by day 1 and exhibited hair follicular sprouting by day 5-7.

    “These cells formed spherical aggregates by day 1 and exhibited hair follicular sprouting by day 5–7 (Figure a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Skin organoids containing hair follicles and sebaceous glands have been successfully regenerated in vitro using mouse and human iPSCs, and replicated typical hair follicle morphogenesis in vitro.

    “Skin organoids containing hair follicles and sebaceous glands have been successfully regenerated in vitro using mouse and human induced pluripotent stem cells (hiPSCs), and these skin organoids also replicated typical hair follicle morphogenesis in vitro.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    HFGs from murine embryonic skin-derived epithelial and mesenchymal layer cells showed highly efficient hair follicle regeneration upon transplantation into nude mice.

    “HFGs from murine embryonic skin-derived epithelial and mesenchymal layer cells showed highly efficient hair follicle regeneration upon transplantation into the skin of nude mice.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The same experiments were repeated with three mice.

    “The same experiments were repeated with three mice.”
    • Also stated in: § Materials and Methods · plain
      “The same experiments were repeated using three different mice.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    To investigate the average number of hair follicle sprouts, 12 cHFOs per condition were used when conducting statistical analysis using Tukey's test.

    “To investigate the average number of hair follicle sprouts, 12 cHFOs per condition were used when conducting a statistical analysis using Tukey’s test.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The Committee on Animal Care and Use of Yokohama National University and the Central Institute for Experimental Animals approved this animal study.

    “The Committee on Animal Care and Use of Yokohama National University (Permit Number: 2019–04 and 2019–06) and the Central Institute for Experimental Animals (Permit Number: 20077) approved this animal study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The study demonstrates the feasibility/potential of using hiPSC-EPCs in HFO cultures as tissue grafts for hair regenerative medicine.

    “this study demonstrates the potential of employing hiPSC-derived ectodermal precursor cells (hiPSC-EPCs) in HFO cultures in hair regenerative medicine.”
    • Also stated in: § Introduction · boosted
      “Our findings demonstrate the feasibility of using hiPSC-EPCs for HFOs as tissue grafts for hair regenerative medicine.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Mouse embryonic mesenchymal cells can substitute for human mesenchymal cells in chimeric HFOs to support hiPSC-derived ectodermal precursor cells and model human HFO formation.
    • Rests on an assumption: The collagen I concentration and culture conditions optimized for mouse cHFOs are suitable for human/mouse chimeric HFOs.

  • Classified as probably not a substantial claim.

    Premisenone given

    Recent advances in stem cell technology have enabled production of hair follicle epithelial and mesenchymal layer stem/precursor cells from hiPSCs.

    “Recent advances in stem cell technology have enabled the production of hair follicle epithelial and mesenchymal layer stem/precursor cells from hiPSCs, and these hiPSC-derived cells were found to contribute to hair follicle regeneration in animal experiments.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Matrigel is not suitable for clinical settings because it is derived from mouse sarcomas and must be replaced with a clinically suitable ECM.

    “Matrigel is not suitable for use in clinical settings because it is derived from mouse sarcomas and must be replaced with a clinically suitable extracellular matrix (ECM).”
    • Also stated in: § Abstract · plain
      “this mouse tumor-derived matrix cannot be applied in human treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The average number of hair shafts generated in the patch assay was calculated from three independent experiments.

    “The average number of hair shafts generated in the patch assay was calculated from three independent experiments.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Statistical significance was defined as p-value <0.05.

    “data were considered statistically significant when the p-value was <0.05.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premiseown data

    High concentrations of collagen I are effective for preparing HFGs using a bioprinter, whereas low concentrations of collagen I may be beneficial for preparing HFOs.

    “In previous studies, we demonstrated that high concentrations of collagen I are effective for preparing HFGs using a bioprinter, whereas low concentrations of collagen I may be beneficial for the preparation of HFOs.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Error bars indicate standard errors calculated from at least three independent experiments.

    “Error bars indicate standard errors calculated from at least three independent experiments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Matrigel is composed of basement membrane extracts, including laminin, collagen IV, heparin sulfate proteoglycans, entactin/nidogen, and various growth factors.

    “Matrigel is composed of basement membrane extracts, including laminin, collagen IV, heparin sulfate proteoglycans, entactin/nidogen, and various growth factors.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Animal experiments were conducted in accordance with the ARRIVE guidelines.

    “Animal experiments were conducted in accordance with the ARRIVE guidelines (https://arriveguidelines.org).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Skin organoid induction involves multiple differentiation steps starting with ectoderm induction, requires a long culture period (4-5 months), and may ultimately induce undifferentiated and unknown cells.

    “However, their induction involves multiple differentiation steps starting with ectoderm induction, which requires a long culture period (4–5 months), and undifferentiated and unknown cells may ultimately be induced.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Gene expression levels were normalized to GAPDH, an experimental control.

    “The expression levels of all genes were normalized to those of GAPDH, an experimental control.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    To use this approach for clinical applications, it is necessary to replace cell sources with human fetal skin-derived epithelial and mesenchymal layer cells, and ethical considerations regarding the use of these cell types are a challenge.

    “However, to use this approach for clinical applications, it is necessary to replace cell sources with human fetal skin-derived epithelial and mesenchymal layer cells, and ethical considerations regarding the use of these cell types are a challenge.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Hair cortex and hair follicle stem cells were included in the hair follicles.

    “suggested that hair cortex and hair follicle stem cells were included in the hair follicles.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Patch assays for regenerating human/mouse chimeric hair follicles are widely used to understand the hair regeneration ability of human epithelial cells.

    “Patch assays for regenerating human/mouse chimeric hair follicles are widely used to understand the hair regeneration ability of human epithelial cells.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductreasoning

    In this assay, mouse mesenchymal layer cells were transplanted as a negative control because mouse hair follicle regeneration occurs when abundant mouse epithelial layer cells are contaminated with the mouse mesenchymal layer cell population.

    “In this assay, mouse mesenchymal layer cells were transplanted as a negative control because mouse hair follicle regeneration occurs when abundant mouse epithelial layer cells are contaminated with the mouse mesenchymal layer cell population.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisecitation

    A previous study showed that hiPSC-mesenchymal cells were differentiated from hiPSCs, which generated hair shafts by cotransplanting with human keratinocytes into mice.

    “A previous study showed that hiPSC-mesenchymal cells were differentiated from hiPSCs, which generated hair shafts by cotransplanting with human keratinocytes into mice.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    hiPSC-derived KRT18-positive EPCs regenerate hair follicles in vivo after transplantation with mouse embryonic skin-derived mesenchymal layer cells.

    “Previous studies have demonstrated that hiPSC-derived cytokeratin 18 (KRT18)-positive EPCs regenerate hair follicles in vivo after transplantation with mouse embryonic skin-derived mesenchymal layer cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    This eliminates the challenges associated with passage-induced loss of function and provides a more reliable source of epithelial cells for HFO preparation.

    “This eliminates the challenges associated with passage-induced loss of function and provides a more reliable source of epithelial cells for HFO preparation.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: hiPSCs can proliferate vigorously while maintaining their stemness and thus do not require further subculturing after differentiation.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    hiPSC-EPCs offer distinct advantages because hiPSCs can proliferate vigorously while maintaining their stemness and thus do not require further subculturing after differentiation.

    “hiPSC-EPCs offer distinct advantages because hiPSCs can proliferate vigorously while maintaining their stemness and thus do not require further subculturing after differentiation.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: hiPSCs can proliferate vigorously while maintaining their stemness and thus do not require further subculturing after differentiation.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    These findings may be beneficial for developing improved hair regenerative strategies.

    “These findings may be beneficial for developing improved hair regenerative strategies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The robust in vitro hair follicular sprouting and successful in vivo hair regeneration observed with cHFOs prepared using hiPSC-EPCs underscores their potential as scalable and efficient cell sources for hair regenerative medicine.

    “The robust in vitro hair follicular sprouting and successful in vivo hair regeneration observed with cHFOs prepared using hiPSC-EPCs underscores their potential as scalable and efficient cell sources for hair regenerative medicine.”
    Quote in the paperSubstantial claim
37 of 37

  • The paper relies on this without support.

    Collagen I is the most abundant ECM in the human body and a low-immunogenic derivative is available in clinical settings.

    “Collagen I is the most abundant ECM in the body, and it has been used in human treatments, including regenerative medicine.”
    “Among these effective components, collagen I is the most abundant ECM in the human body, and a low-immunogenic derivative of collagen obtained by the removal of the N- and C-terminal telopeptide components is available in clinical settings.”

  • The paper relies on this without support.

    Mouse embryonic mesenchymal cells can substitute for human mesenchymal cells in chimeric HFOs to support hiPSC-derived ectodermal precursor cells and model human HFO formation.

    “hiPSCs were differentiated into human ectodermal precursor cells and subsequently used to generate human/mouse chimeric HFOs with mouse embryonic mesenchymal cells.”
    “Although another approach to induce human mesenchymal layer cells from hiPSCs is necessary to generate fully human HFOs, this study demonstrates the potential of employing hiPSC-derived ectodermal precursor cells (hiPSC-EPCs) in HFO cultures in hair regenerative medicine.”

  • The paper relies on this without support.

    The collagen I concentration and culture conditions optimized for mouse cHFOs are suitable for human/mouse chimeric HFOs.

    “The hiPSC-EPCs (1 × 104 cells/mL) and mouse mesenchymal layer cells (1 × 104 cells/mL) were suspended in 0.2 mL of DMEM/F-12 containing 2% v/v Matrigel or 24 μg/mL collagen I and seeded in 96-well spheroid formation plates.”
    “Based on these results, we decided to use 24 μg/mL collagen I concentration and 6 days of culture prior to transplantation in the subsequent experiments.”

  • The paper relies on this without support.

    Adult cells may possess a lower hair follicle regeneration capacity, whereas fetal cells have a higher regenerative potential but pose ethical concerns.

    “Adult cells can be harvested from the hair follicles of patients with alopecia but may possess a lower hair follicle regeneration capacity, whereas fetal cells have a higher regenerative potential but pose ethical concerns.”

  • The paper relies on this without support.

    The regenerative capacity of fetal epithelial layer cells diminishes after multiple passages in vitro.

    “However, the regenerative capacity of fetal epithelial layer cells diminishes after multiple passages in vitro, although proliferation is often required to obtain a sufficient number of cells for use in hair regenerative medicine.”

  • The paper relies on this without support.

    hiPSCs can proliferate vigorously while maintaining their stemness and thus do not require further subculturing after differentiation.

    “hiPSCs can proliferate vigorously while maintaining their stemness and thus do not require further subculturing after differentiation.”

  • The paper relies on this without support.

    Potential limitations to the use of human iPSCs include epigenetic memory, high development costs, and time-consuming differentiation.

    “potential limitations to the use of human iPSCs remain, including epigenetic memory, the high development costs, and time-consuming differentiation.”

  • The paper relies on this without support.

    Transplantation of undifferentiated hiPSCs can result in teratoma formations.

    “The transplantation of undifferentiated hiPSCs can result in teratoma formations.”
8 of 8

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Control epithelial cells are described as both adult and fetal

    Minor

    The results identify the control cells as human adult skin-derived epithelial cells, whereas the methods and Figure 5 identify the corresponding control as human fetal epithelial cells. This changes which cell source the reported negative control represents.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. An L., 2018, Am. J. Transl. Res., 10, 3689
  2. 10.1038/srep42777 · DOI

Cited by

Sorted by citations

Authors
Kageyama, T., Anakama, R., Hamano, S., Tu, S., Migita, Y., Asaba, T., Nanmo, A., Ishikawa, K., Yan, L., Seo, J., & Fukuda, J.
Affiliations
Yokohama National University (JP)
Corresponding author
Fukuda, Junji
ORCID
Venue
ACS Biomaterials Science & Engineering
Publisher
American Chemical Society (ACS)
Published
2026-02-10
Volume
12
Issue
3
Pages
1704-1714
ISSN
2373-9878 (ISSN-L)
DOI
10.1021/acsbiomaterials.5c01780
PMC
PMC12976999
OpenAlex
W7128495693
Semantic Scholar
f128b3972f96e3a11816e4d5e54452c345926b58
Cited by
6
References
49
Citations by year
2026: 6
FWCI
39.94
Type
journal article
Language
en
Open access
Licence
Locations
  • ACS Biomaterials Science & Engineering (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • Takeda Science Foundation
  • Sekisui Chemical
  • Japan Agency for Medical Research and Development (23bm1123031h0001)
  • Japan Society for the Promotion of Science (23H01771, 23K13614)
  • Kanagawa Institute of Industrial Science and Technology
  • Mochida Memorial Foundation for Medical and Pharmaceutical Research
  • Kao Melanin Workshop
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
human induced pluripotent stem cells, hair regrowth, Matrigel, epithelial-mesenchymal interactions, tissue grafts
MeSH terms
Animals, Cell Differentiation, Collagen, Ectoderm, Humans, Organoids, Proteoglycans, Regeneration, Hair Follicle, Regenerative Medicine, Mice, Induced Pluripotent Stem Cells

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