CoChat
Sign Up
Cited by 15Dermatology and Skin DiseasesContact Dermatitis and AllergiesAnimal testing and alternatives

Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models

Open access
Atwood, Scott X., Plikus, Maksim V.·2021·Experimental Dermatology
DOI 10.1111/exd.14296PMC PMC8142902
Open this paper in CoChat — free account

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/exd.14296

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The presence of abnormal cell states and altered differentiation patterns in organoid cultures have been observed in a variety of tissues, including skin, using more conventional methods.

    “The presence of abnormal cell states and altered differentiation patterns in organoid cultures have been observed in a variety of tissues,4 including skin,9 using more conventional methods.”

    From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [9]

    In “What organotypic cultures can and can’t do” (page unavailable), the paper says 3D skin cultures can lack a normal stratum corneum, epidermal barrier, or lipid composition. It also reports impaired expression of differentiation markers, but that finding concerns monolayer keratinocyte cultures, not organoids. The paper therefore supports limitations in skin cultures, but not the specific claim that abnormal cell states and altered differentiation patterns were observed in skin organoids. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • HSE composition and culture conditions vary greatly from lab to lab, which can affect interpretation of similar experiments.

    “their composition and culture conditions vary greatly from lab to lab, which can affect interpretation of similar experiments.”

    From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [9]

  • HSEs lack many components of the in vivo system, such as vasculature and immune cells, which limits the size of cultures and their response to experimental stimuli.

    “Many components of the in vivo system are lacking, such as vasculature and immune cells, which limits the size of cultures and their response to experimental stimuli.”

    From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [9]

Self-check

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

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 79

  1. [1]Zhang B, He M, Rachmin I, Melanocortin 1 receptor is dispensable for acute stress induced hair graying in mice. Exp Dermatol. 2020. PMC8016727 33382172
  2. [2]Chovatiya G, Ghuwalewala S, Walter LD, Cosgrove BD, Tumbar T. High-resolution single-cell transcriptomics reveals heterogeneity of self-renewing hair follicle stem cells. Exp Dermatol. 2020. PMC8016723 33319418
  3. [3]Wang Z, Chen Y, Chen M, Zhang Y. Overexpression of Fgf8 in the epidermis inhibits hair follicle development. Exp Dermatol. 2020. 33141445
  4. [4]Nicu C, Wikramanayake TC, Paus R. Clues that mitochondria are involved in the hair cycle clock: MPZL3 regulates entry into progression of murine hair follicle cycling. Exp Dermatol. 2020; 29(12): 1243– 1249. 33040410
  5. [5]Swanson JB, Vagnozzi AN, Veniaminova NA, Wong SY. Loss of Gata6 causes dilation of the hair follicle canal sebaceous duct. Exp Dermatol. 2019; 28(4): 345– 349. 30033638 PMC6529183
  6. [6]Jiang TX, Harn HI, Ou KL, Lei M, Chuong CM. Comparative regenerative biology of spiny (Acomys cahirinus) laboratory (Mus musculus) mouse skin. Exp Dermatol. 2019; 28(4): 442– 449. 30734959 PMC6488381
  7. [7]Maden M, Brant JO. Insights into the regeneration of skin from Acomys, the spiny mouse. Exp Dermatol. 2019; 28(4): 436– 441. 30457673
  8. [8]Kaymakcalan OE, Abadeer A, Goldufsky JW, Topical alpha-gal nanoparticles accelerate diabetic wound healing. Exp Dermatol. 2020; 29(4): 404– 413. 32027409
  9. [9]Gilhar A, Reich K, Keren A, Kabashima K, Steinhoff M, Paus R. Mouse models of atopic dermatitis: a critical reappraisal. Exp Dermatol. 2020. 33368555
  10. [10]Smith L, Gatault S, Casals-Diaz L, House dust mite-treated PAR2 over-expressor mouse: A novel model of atopic dermatitis. Exp Dermatol. 2019; 28(11): 1298– 1308. 31487753
  11. [11]Fu X, Hong C. Osthole attenuates mouse atopic dermatitis by inhibiting thymic stromal lymphopoietin production from keratinocytes. Exp Dermatol. 2019; 28(5): 561– 567. 30825337
  12. [12]Tang L, Cao X, Li X, Ding H. Topical application with conjugated linoleic acid ameliorates 2, 4-dinitrofluorobenzene-induced atopic dermatitis-like lesions in BALB/c mice. Exp Dermatol. 2020. 33206422
  13. [13]Kake T, Imai M, Takahashi N. Effects of beta-carotene on oxazolone-induced atopic dermatitis in hairless mice. Exp Dermatol. 2019; 28(9): 1044– 1050. 31287602
  14. [14]Porras M, Gomez LA, Perez JJ. Anti-inflammatory Effect of Amygdalin Analogs Following Topical Administration on the TPA-Induced Irritant Contact Dermatitis Model in Mice. Exp Dermatol. 2021. 33449397
  15. [15]Fukuyama T, Nakamura Y, Kanemaru K, Phospholipase Cgamma1 is required for normal irritant contact dermatitis responses sebaceous gl homeostasis. Exp Dermatol. 2019; 28(9): 1051– 1057. 31338881
  16. [16]Frempah B, Luckett-Chastain LR, Gallucci RM. IL6Ralpha function in myeloid cells modulates the inflammatory response during irritant contact dermatitis. Exp Dermatol. 2019; 28(8): 948– 955. 31165501
  17. [17]Kiss B, Szanto M, Hegedus C, Poly(ADP-ribose) polymerase-1 depletion enhances the severity of inflammation in an imiquimod-induced model of psoriasis. Exp Dermatol. 2020; 29(1): 79– 85. 31755591
  18. [18]Yi F, Zheng X, Fang F, Zhang J, Zhou B, Chen X. ALA-PDT alleviates the psoriasis by inhibiting JAK signalling pathway. Exp Dermatol. 2019; 28(11): 1227– 1236. 31386778
  19. [19]Son M, Park J, Oh S, Radiofrequency irradiation attenuates angiogenesis inflammation in UVB-induced rosacea in mouse skin. Exp Dermatol. 2020. 32434270
  20. [20]Yang X, Daifallah AEM, Shankar S, Topical kinase inhibitors induce regression of cutaneous squamous cell carcinoma. Exp Dermatol. 2019; 28(5): 609– 613. 30762245 PMC6520110
  21. [22]Smits JPH, Dirks RAM, Qu J, Terminal keratinocyte differentiation in vitro is associated with a stable DNA methylome. Exp Dermatol. 2020. PMC8359404 32681572
  22. [23]Jeriha J, Kolundzic N, Khurana P, Markers for Ca(++) -induced terminal differentiation of keratinocytes in vitro under defined conditions. Exp Dermatol. 2020; 29(12): 1238– 1242. 32978827
  23. [24]Emmert H, Fonfara M, Rodriguez E, Weidinger S. NADPH oxidase inhibition rescues keratinocytes from elevated oxidative stress in a 2D atopic dermatitis psoriasis model. Exp Dermatol. 2020; 29(8): 749– 758. 32640089
  24. [25]Chen J, Liu K, Liu Y, Wang X, Zhang Z. Targeting mTORC1/2 with OSI-027 inhibits proliferation migration of keloid keratinocytes. Exp Dermatol. 2019; 28(3): 270– 275. 30650200
  25. [26]Xu P, Xue YN, Ji HH, Tan C, Guo S. H2 O2 -induced oxidative stress disrupts mitochondrial functions impairs migratory potential of human epidermal melanocytes. Exp Dermatol. 2020; 29(8): 733– 741. 32580253
  26. [27]Lv J, Fu Y, Cao Y, Isoliquiritigenin inhibits melanogenesis, melanocyte dendricity melanosome transport by regulating ERK-mediated MITF degradation. Exp Dermatol. 2020; 29(2): 149– 157. 31785162
  27. [28]Jimbo H, Nagai H, Fujiwara S, Shimoura N, Nishigori C. Fas-FasL interaction in cytotoxic T cell-mediated vitiligo: The role of lesional expression of tumor necrosis factor-alpha interferon-gamma in Fas-mediated melanocyte apoptosis. Exp Dermatol. 2020; 29(1): 61– 70. 31675451
  28. [29]Tam I, Dzierzega-Lecznar A, Stepien K. Differential expression of inflammatory cytokines chemokines in lipopolysaccharide-stimulated melanocytes from lightly darkly pigmented skin. Exp Dermatol. 2019; 28(5): 551– 560. 30801846
  29. [30]Yoshimoto S, Ohagi Y, Yoshida M, Placental extracts regulate melanin synthesis in normal human melanocytes with alterations of mitochondrial respiration. Exp Dermatol. 2019; 28 Suppl 1:50–54. 30698880
  30. [31]Arndt S, Lissner C, Unger P, Baumler W, Berneburg M, Karrer S. Biological effects of a new ultraviolet A1 prototype based on light-emitting diodes on the treatment of localized scleroderma. Exp Dermatol. 2020; 29(12): 1199– 1208. 32592187
  31. [32]Ham S, Harrison C, de Kretser D, Wallace EM, Southwick G, Temple-Smith P. Potential treatment of keloid pathogenesis with follistatin 288 by blocking the activin molecular pathway. Exp Dermatol. 2020. 33119185
  32. [33]Macarak EJ, Wermuth PJ, Rosenbloom J, Uitto J. Keloid disorder: Fibroblast differentiation gene expression profile in fibrotic skin diseases. Exp Dermatol. 2021; 30(1): 132– 145. 33211348
  33. [34]Lee YS, Liang YC, Wu P, STAT3 signalling pathway is implicated in keloid pathogenesis by preliminary transcriptome open chromatin analyses. Exp Dermatol. 2019; 28(4): 480– 484. 30916811 PMC6488383
  34. [35]Ogata Y, Yamada T, Hasegawa S, SASP-induced macrophage dysfunction may contribute to accelerated senescent fibroblast accumulation in the dermis. Exp Dermatol. 2021; 30(1): 84– 91. 33010063
  35. [37]de Jesus-Gil C, Ruiz-Romeu E, Ferran M, IL-15 IL-23 synergize to trigger Th17 response by CLA(+) T cells in psoriasis. Exp Dermatol. 2020. 32476200
  36. [39]Lee V, Singh G, Trasatti JP, Design fabrication of human skin by three-dimensional bioprinting. Tissue Eng Part C Methods. 2014; 20(6): 473– 484. 24188635 PMC4024844
  37. [40]Zouboulis CC, Yoshida GJ, Wu Y, Xia L, Schneider MR. Sebaceous gl: Milestones of 30-year modelling research dedicated to the “ brain of the skin”. Exp Dermatol. 2020. 32875660
  38. [41]Weber EL, Woolley TE, Yeh CY, Ou KL, Maini PK, Chuong CM. Self-organizing hair peg-like structures from dissociated skin progenitor cells: New insights for human hair follicle organoid engineering Turing patterning in an asymmetric morphogenetic field. Exp Dermatol. 2019; 28(4): 355– 366. 30681746 PMC6488368
  39. [42]Bjerke DL, Li R, Price JM, The vitamin A ester retinyl propionate has a unique metabolic profile higher retinoid-related bioactivity over retinol retinyl palmitate in human skin models. Exp Dermatol. 2020. 33098193
  40. [43]Percoco G, Patatian A, Eudier F, Impact of cigarette smoke on physical-chemical molecular proprieties of human skin in an ex vivo model. Exp Dermatol. 2020. 32939877
  41. [44]Olah A, Alam M, Cheret J, Mitochondrial energy metabolism is negatively regulated by cannabinoid receptor 1 in intact human epidermis. Exp Dermatol. 2020. 32367548
  42. [45]Nicu C, Hardman JA, Pople J, Paus R. Do human dermal adipocytes switch from lipogenesis in anagen to lipophagy lipolysis during catagen in the human hair cycle? Exp Dermatol. 2019; 28(4): 432– 435. 30776154
  43. [46]Marconi A, Quadri M, Saltari A, Pincelli C. Progress in melanoma modelling in vitro. Exp Dermatol. 2018; 27(5): 578– 586. 29697862
  44. [47]Groeber F, Engelhardt L, Lange J, A first vascularized skin equivalent as an alternative to animal experimentation. ALTEX 2016; 33(4): 415– 422. 27180196
  45. [48]Niehues H, Bouwstra JA, El Ghalbzouri A, Brner JM, Zeeuwen P, van den Bogaard EH. 3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function. Exp Dermatol. 2018; 27(5): 501– 511. 29518287
  46. [49]Cheret J, Ponce L, Le Gall-Ianotto C, Bertolini M, Paus R. Re-innervation of human skin by rat dorsal root ganglia permits to study interactions between sensory nerve fibres native human dermal mast cells ex vivo. Exp Dermatol. 2020. 33247473
  47. [50]Sciezynska A, Nogowska A, Sikorska M, Isolation culture of human primary keratinocytes-a methods review. Exp Dermatol. 2019; 28(2): 107– 112. 30548893
  48. [51]Bock C, Beerman I, Lien WH, DNA methylation dynamics during in vivo differentiation of blood skin stem cells. Mol Cell. 2012; 47(4): 633– 647. 22841485 PMC3428428
  49. [52]Sen GL, Reuter JA, Webster DE, Zhu L, Khavari PA. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature. 2010; 463(7280): 563– 567. 20081831 PMC3050546
  50. [53]Giri PS, Dwivedi M, Begum R. Decreased suppression of CD8(+) CD4(+) T cells by peripheral regulatory T cells in generalized vitiligo due to reduced NFATC1 FOXP3 proteins. Exp Dermatol. 2020; 29(8): 759– 775. 32682346
  51. [54]Portugal-Cohen M, Cohen D, Ish-Shalom E, Laor-Costa Y, Ma’or Z. Dead Sea minerals: New findings on skin the biology beyond. Exp Dermatol. 2019; 28(5): 585– 592. 30903724
  52. [55]Bae IH, Lee ES, Yoo JW, Mannosylerythritol lipids inhibit melanogenesis via suppressing ERK-CREB-MiTF-tyrosinase signalling in normal human melanocytes a three-dimensional human skin equivalent. Exp Dermatol. 2019; 28(6): 738– 741. 30408247
  53. [56]Mi T, Dong Y, Santhanam U, Huang N. Niacinamide 12-hydroxystearic acid prevented benzo(a) pyrene squalene peroxides induced hyperpigmentation in skin equivalent. Exp Dermatol. 2019; 28(6): 742– 746. 30339718
  54. [57]Emmert H, Rademacher F, Glaser R, Harder J. Skin microbiota analysis in human 3D skin models-” Free your mice”. Exp Dermatol. 2020. 32748435
  55. [58]Khmaladze I, Butler E, Fabre S, Gillbro JM. Lactobacillus reuteri DSM 17938-A comparative study on the effect of probiotics lysates on human skin. Exp Dermatol. 2019; 28(7): 822– 828. 31021014
  56. [59]Katsuyama Y, Taira N, Tsuboi T, Yoshioka M, Okano Y, Masaki H. 3-O-Laurylglyceryl ascorbate improves the development of sensitive skin through the reduction of oxidative stress. Exp Dermatol. 2019; 28 Suppl 1:64–68. 30698879
  57. [60]Huth S, Marquardt Y, Huth L, Molecular effects of photon irradiation subsequent aftercare treatment with dexpanthenol-containing ointment or liquid in 3D models of human skin non-keratinized oral mucosa. Exp Dermatol. 2021. 33403711
  58. [61]Sanchez J, Le Jan S, Muller C, Matrix remodelling MMP expression/activation are associated with hidradenitis suppurativa skin inflammation. Exp Dermatol. 2019; 28(5): 593– 600. 30903721
  59. [62]Yoshida A, Yamamoto K, Ishida T, Sunitinib decreases the expression of KRT6A SERPINB1 in 3D human epidermal models. Exp Dermatol. 2020. 33135264
  60. [63]Lee WJ, Lee JL, Chang SE, Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib sunitinib. Br J Dermatol. 2009; 161(5): 1045– 1051. 19558553
  61. [64]Wang P, Tan G, Zhu M, Li W, Zhai B, Sun X. H-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review meta-analysis. Expert Rev Gastroenterol Hepatol. 2018; 12(1): 1– 8. 28847184
  62. [65]Lacouture ME, Reilly LM, Gerami P, Guitart J. H foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib sunitinib. Ann Oncol. 2008; 19(11): 1955– 1961. 18550575
  63. [66]Dreno B What is new in the pathophysiology of acne, an overview. J Eur Acad Dermatol Venereol. 2017; 31 Suppl 5:8–12. 28805938
  64. [67]Zouboulis CC. Endocrinology immunology of acne: Two sides of the same coin. Exp Dermatol. 2020; 29(9): 840– 859. 32779248
  65. [68]Josse G, Mias C, Le Digabel J, High bacterial colonization lipase activity in microcomedones. Exp Dermatol. 2020; 29(2): 168– 176. 31863492 PMC7586799
  66. [69]Moradi Tuchayi S, Makrantonaki E, Ganceviciene R, Dessinioti C, Feldman SR, Zouboulis CC. Acne vulgaris. Nat Rev Dis Primers. 2015; 1: 15029. 27189872
  67. [70]Jasson F, Nagy I, Knol AC, Zuliani T, Khammari A, Dreno B. Different strains of Propionibacterium acnes modulate differently the cutaneous innate immunity. Exp Dermatol. 2013; 22(9): 587– 592. 23947673
  68. [71]Ottaviani M, Alestas T, Flori E, Mastrofrancesco A, Zouboulis CC, Picardo M. Peroxidated squalene induces the production of inflammatory mediators in HaCaT keratinocytes: a possible role in acne vulgaris. J Invest Dermatol. 2006; 126(11): 2430– 2437. 16778793
  69. [72]Laclaverie M, Rouaud-Tinguely P, Grimaldi C, Development characterization of a 3D in vitro model mimicking acneic skin. Exp Dermatol. 2020. 33354825
  70. [73]Zheng Y, Du X, Wang W, Boucher M, Parimoo S, Stenn K. Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells. J Invest Dermatol. 2005; 124(5): 867– 876. 15854024
  71. [74]Morris RJ, Liu Y, Marles L, Capturing profiling adult hair follicle stem cells. Nat Biotechnol. 2004; 22(4): 411– 417. 15024388
  72. [75]Paik SH, Choi SJ, Jang S, Jo SJ, Kim KH, Kwon O. Skin equivalent assay: An optimized method for testing for hair growth reconstitution capacity of epidermal dermal cells. Exp Dermatol. 2019; 28(4): 367– 373. 30702167
  73. [77]Philpott MP. Culture of the human pilosebaceous unit, hair follicle sebaceous gl. Exp Dermatol. 2018; 27(5): 571– 577. 29693730
  74. [78]Wang ECE, Higgins CA. Immune cell regulation of the hair cycle. Exp Dermatol. 2020; 29(3): 322– 333. 31903650
  75. [79]Kwack MH, Seo CH, Gangadaran P, Exosomes derived from human dermal papilla cells promote hair growth in cultured human hair follicles augment the hair-inductive capacity of cultured dermal papilla spheres. Exp Dermatol. 2019; 28(7): 854– 857. 30924959
  76. [80]Kim JE, Oh JH, Woo YJ, Jung JH, Jeong KH, Kang H. Effects of mesenchymal stem cell therapy on alopecia areata in cellular hair follicle organ culture models. Exp Dermatol. 2020; 29(3): 265– 272. 30372797
  77. [81]Buscone S, Mardaryev AN, Westgate GE, Uzunbajakava NE, Botchkareva NV. Cryptochrome 1 is modulated by blue light in human keratinocytes exerts positive impact on human hair growth. Exp Dermatol. 2020. 33141439
  78. [82]Nicu C, O’Sullivan JDB, Ramos R, Dermal adipose tissue secretes HGF to promote human hair growth pigmentation. Journal of Investigative Dermatology. 33493531
  79. [83]Nakashima C, Ishida Y, Kitoh A, Otsuka A, Kabashima K. Interaction of peripheral nerves mast cells, eosinophils, basophils in the development of pruritus. Exp Dermatol. 2019; 28(12): 1405– 1411. 31365150

Cited by

Sorted by citations

Authors
Atwood, S. X., & Plikus, M. V.
Affiliations
University of California, Irvine (US)
Corresponding author
  • Atwood, Scott X.
  • Plikus, Maksim V.
ORCID
Venue
Experimental Dermatology
Publisher
Wiley
Published
2021-02-10
Volume
30
Issue
3
Pages
298-303
ISSN
  • 0906-6705 (ISSN-L)
  • 1600-0625
DOI
10.1111/exd.14296
PMC
PMC8142902
OpenAlex
W3128880568
Cited by
15
References
4
Citations by year
2026: 10 · 2025: 2 · 2023: 2 · 2022: 1
FWCI
0.67
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Experimental Dermatology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • LEO Fondet (LF-OC-20-000611, LF-AW_RAM-19-400008)
  • National Cancer Institute (R01CA237563)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01AR073159, R01AR069653, P30AR075047)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
  • Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Keywords
in vitro skin model, ex vivo skin model, skin biology, skin health
MeSH terms
Humans, Models, Biological, Organ Culture Techniques, Organoids, Skin, Skin Diseases, Skin Physiological Phenomena, Hair Follicle

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review