Cited by 25Hair Growth and DisordersSkin Protection and AgingSkin and Cellular Biology Research

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids

Open access
Kim, Min-Ji, Ahn, Hee-Jin, Kong, Dasom, Lee, Seunghee, Kim, Da-Hyun, Kang, Kyung-Sun·2024·Journal of Tissue Engineering

Abstract

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

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 · 10.1177/20417314241248753

Cites

11 of 11 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?

  • Transient activation of WNT signalling during organoid development suppresses ectopic cartilage formation and promotes generation of large, correctly oriented skin organoids suitable for modelling solar UV-induced damage and repair.

    “Transient activation of WNT signalling during organoid development suppresses ectopic cartilage formation and promotes the generation of large, correctly oriented skin organoids suitable for modelling solar UV-induced damage and repair 16 .”

    From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [16]

    The Methods (page unavailable) say a WNT agonist was added during organoid development to prevent off-target cartilage differentiation and increase organoid diameter. The Discussion (page unavailable) attributes the planar, skin-like arrangement to cutting the organoids and using an air–liquid interface, not to WNT activation alone. The paper uses those organoids to model solar UV damage and a potential treatment, but does not establish that WNT activation itself produces their orientation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Previous studies have shown that skin organoids can generate stratified epidermal and dermal compartments, but they generally fail to establish vascular structures, a defining feature of native human skin.

    “Previous studies have shown that skin organoids can generate stratified epidermal and dermal compartments, but they generally fail to establish vascular structures, a defining feature of native human skin 13,16 .”

    From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [16]

    The Results (Characterization of iPSC-derived hair-bearing SkOs; page unavailable) describe organoids with a stratified epidermis and dermis. The paper does not state that skin organoids generally fail to form vascular structures; searches for vascular structures and vascularization found no supporting passage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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: 65

  1. [1]Armstrong BK Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol B Biol 2001; 63: 8– 18. 11684447
  2. [2]Nogueira A Joekes I Dicelio L. About photo-damage of human hair. Photochem Photobiol Sci 2006; 5: 165– 169. 16465301
  3. [3]Zhai X Gong M Peng Y, et al. Effects of UV induced-photoaging on the hair follicle cycle of C57BL6/J mice. Clin Cosmet Investi Dermatol 2021; 14: 527– 539. PMC8140904 34040410
  4. [4]Merin K Shaji M Kameswaran R. A review on sun exposure and skin diseases. Indian J Dermatol 2022; 67: 625. PMC9971785 36865856
  5. [6]Sutterby E Thurgood P Baratchi S, et al. Evaluation of in vitro human skin models for studying effects of external stressors and stimuli and developing treatment modalities. View 2022; 3: 20210012.
  6. [7]Zhang JY. Chapter 15-Animal models of skin disorders. In: Conn PM (ed) Animal Models for the Study of Human Disease (Second Edition). Academic Press, 2017, pp. 357– 375.
  7. [9]Danilenko DM Phillips GDL Diaz D. In vitro skin models and their predictability in defining normal and disease biology, pharmacology, and toxicity. Toxicol Pathol 2016; 44: 555– 563. 26940714
  8. [10]Wufuer M Lee G Hur W, et al. Skin-on-a-chip model simulating inflammation, edema and drug-based treatment. Sci Rep 2016; 6: 37471. 27869150 PMC5116589
  9. [11]Yan W-C Davoodi P Vijayavenkataraman S, et al. 3D bioprinting of skin tissue: from pre-processing to final product evaluation. Adv Drug Deliv Rev 2018; 132: 270– 295. 30055210
  10. [14]Jung S-y You HJ Kim M-J, et al. Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes. Iscience 2022; 25: 105150. 36193049 PMC9526179
  11. [15]Kalluri RL Valerie S. The biology, function, and biomedical applications of exosomes. Science 2020; 367: eaau6977. PMC7717626 32029601
  12. [16]Janockova J Slovinska L Harvanova D, et al. New therapeutic approaches of mesenchymal stem cells-derived exosomes. J Biomed Sci 2021; 28: 1– 26. 34030679 PMC8143902
  13. [17]Li M Li S Du C, et al. Exosomes from different cells: Characteristics, modifications, and therapeutic applications. Eur J Med Chem. 2020; 207: 112784. 33007722
  14. [18]Cho BS Kim JO Ha DH, et al. Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res Ther 2018; 9: 1– 5. 29996938 PMC6042362
  15. [19]Shin K-O Ha DH Kim JO, et al. Exosomes from human adipose tissue-derived mesenchymal stem cells promote epidermal barrier repair by inducing de novo synthesis of ceramides in atopic dermatitis. Cells 2020; 9: 680. 32164386 PMC7140723
  16. [20]Zhang B Wang M Gong A, et al. HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing. Stem cells 2015; 33: 2158– 2168. 24964196
  17. [21]Rani S Ritter T. The exosome – A naturally secreted nanoparticle and its application to wound healing. Adv Mater 2016; 28: 5542– 5552. 26678528
  18. [22]Kim Y-J Mi Yoo S Park HH, et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin. Biochem Biophys Res Commun 2017; 493: 1102– 1108. 28919421
  19. [23]Liang J-X Liao X Li S-H, et al. Antiaging properties of exosomes from adipose-derived mesenchymal stem cells in photoaged rat skin. BioMed Res Int 2020; 2020: 6406395. 33415151 PMC7769639
  20. [24]Kim JE Heo YS Lee KW. Osajin inhibits solar UV-induced cyclooxygenase-2 expression through direct inhibition of RSK2. J Cell Biochem 2017; 118: 4080– 4087. 28409880
  21. [25]Biniek K Levi K Dauskardt RH. Solar UV radiation reduces the barrier function of human skin. Proc Natl Acad Sci USA 2012; 109: 17111– 17116. 23027968 PMC3479513
  22. [26]Pittayapruek P Meephansan J Prapapan O, et al. Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. Int J Mol Sci 2016; 17: 868. 27271600 PMC4926402
  23. [27]Lee SJ Lee KB Son YH, et al. Transglutaminase 2 mediates UV-induced skin inflammation by enhancing inflammatory cytokine production. Cell Death Dis 2017; 8: e3148. PMC5680918 29072680
  24. [28]Zhang YL Yan JJ Li ZJ, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate psoriasis-like skin inflammation. J Interf Cytok Res 2022; 42: 8– 18. 35041513
  25. [29]Bahta AW Farjo N Farjo B, et al. Premature senescence of balding dermal papilla cells is associated with p16 expression. J Invest Dermatol 2008; 128: 1088– 1094. 17989730
  26. [31]Tavana O Benjamin CL Puebla-Osorio N, et al. Absence of p53-dependent apoptosis leads to UV radiation hypersensitivity, enhanced immunosuppression and cellular senescence. Cell Cycle 2010; 9: 3328– 3336. 20703098 PMC3041166
  27. [32]Müller K Meineke V. Radiation-induced alterations in cytokine production by skin cells. Exp Hematol 2007; 35: 96– 104. 17379094
  28. [33]Yu H Lin LB Zhang ZQ, et al. Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Tar 2020; 5: 209. PMC7506548 32958760
  29. [34]Piipponen M Li DQ Landén NX. The Immune functions of keratinocytes in skin wound healing. Int J Mol Sci 2020; 21: 8790. 33233704 PMC7699912
  30. [35]Wang JN Duan ZM Chen X, et al. The immune function of dermal fibroblasts in skin defence against pathogens. Exp Dermatol 2023; 32: 1326– 1333. 37387265
  31. [36]Bora NS Mazumder B Mandal S, et al. Amelioration of UV radiation-induced photoaging by a combinational sunscreen formulation via aversion of oxidative collagen degradation and promotion of TGF-β-Smad-mediated collagen production (Retraction of Vol 127, Pg 261, 2019). Eur J Pharm Sci 2022; 177: 106245. 30414837
  32. [37]Gherardini J Wegner J Chéret J, et al. Transepidermal UV radiation of scalp skin induces hair follicle damage that is alleviated by the topical treatment with caffeine. Int J Cosmetic Sci 2019; 41: 164– 182. PMC6850087 30746733
  33. [38]Lee J Rhee MH Kim E, et al. BAY 11-7082 is a broad-spectrum inhibitor with anti-inflammatory activity against multiple targets. Mediat Inflamm 2012; 2012: 416036. PMC3382285 22745523
  34. [39]Haga M Okada M. Systems approaches to investigate the role of NF-kappaB signaling in aging. Biochem J 2022; 479: 161– 183. 35098992 PMC8883486
  35. [40]Gruber F Kremslehner C Eckhart L, et al. Cell aging and cellular senescence in skin aging – Recent advances in fibroblast and keratinocyte biology. Exp Gerontol 2020; 130: 110780. 31794850
  36. [41]Kang C Xu Q Martin TD, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 2015; 349: aaa5612. PMC4942138 26404840
  37. [42]Takeo M Lee W Ito M. Wound healing and skin regeneration. Cold Spring Harb Perspect Med 2015; 5: a023267. PMC4292081 25561722
  38. [43]Xu Y Wu X Zhang Y, et al. Engineered artificial skins: current construction strategies and applications. Eng Regen 2023; 4: 438– 450.
  39. [44]Abaci HE Coffman A Doucet Y, et al. Tissue engineering of human hair follicles using a biomimetic developmental approach. Nat Commun 2018; 9: 5301. 30546011 PMC6294003
  40. [45]Miyake T Shimada M. 3D organoid culture using skin keratinocytes derived from human induced pluripotent stem cells. Methods Mol Biol 2022; 2454: 285– 295. 33689165
  41. [46]Ma J Liu J Gao D, et al. Establishment of human pluripotent stem cell-derived skin organoids enabled pathophysiological model of SARS-CoV-2 infection. Adv Sci 2022; 9: e2104192. PMC8895131 34971128
  42. [49]Ittycheri A Lipsky ZW Hookway TA, et al. Ultraviolet light induces mechanical and structural changes in full thickness human skin. J Mech Behav Biomed Mater 2023; 143: 105880. 37172426
  43. [50]Salminen A Kaarniranta K Kauppinen A. Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin. Inflamm Res 2022; 71: 817– 831. 35748903 PMC9307547
  44. [52]Laszlo CF Wu S. Mechanism of UV-induced IkappaBalpha-independent activation of NF-kappaB. Photochem Photobiol 2008; 84: 1564– 1568. 18627520 PMC2743866
  45. [53]Pillai S Oresajo C Hayward J. Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation – a review. Int J Cosmet Sci 2005; 27: 17– 34. 18492178
  46. [55]Sharma MR Werth B Werth VP. Animal models of acute photodamage: comparisons of anatomic, cellular and molecular responses in C57BL/6J, SKH1 and Balb/c mice. Photochem Photobiol 2011; 87: 690– 698. 21332482 PMC3928020
  47. [56]Lin MF Liu XR Wang XE, et al. A comparative study of skin changes in different species of mice in chronic photoaging models. Int J Mol Sci 2023; 24: 10812. 37445996 PMC10341798
  48. [57]Bacqueville D Douki T Duprat L, et al. A new hair follicle-derived human epidermal model for the evaluation of sunscreen genoprotection. J Photochem Photobiol B 2015; 151: 31– 38. 26163483
  49. [58]Natarajan VT Ganju P Ramkumar A, et al. Multifaceted pathways protect human skin from UV radiation. Nat Chem Biol 2014; 10: 542– 551. 24937072
  50. [59]Qin JZ Chaturvedi V Denning MF, et al. Regulation of apoptosis by p53 in UV-irradiated human epidermis, psoriatic plaques and senescent keratinocytes. Oncogene 2002; 21: 2991– 3002. 12082529
  51. [60]Lu Z Fischer TW Hasse S, et al. Profiling the response of human hair follicles to ultraviolet radiation. J Invest Dermatol 2009; 129: 1790– 1804. 19158839
  52. [61]Piérard-Franchimont C Quatresooz P Piérard GE. Effect of UV radiation on scalp and hair growth, In: Trüeb RM Tobin DJ (eds) Aging Hair. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010, pp.113–121 2010.
  53. [62]Xu JM Weng ZP Arumugam A, et al. Hair follicle disruption facilitates pathogenesis to UVB-induced cutaneous inflammation and basal cell carcinoma development in mice. Am J Pathol 2014; 184: 1529– 1540. 24631180 PMC4005987
  54. [63]Zhang B Zhao Y Cai ZM, et al. Early stage alopecia areata is associated with inflammation in the upper dermis and damage to the hair follicle infundibulum. Australas J Dermatol 2013; 54: 184– 191. 23808570
  55. [64]Yang GH Lee YB Kang D, et al. Overcome the barriers of the skin: exosome therapy. Biomater Res 2021; 25: 22. 34217362 PMC8254055
  56. [65]Han JX Wu T Jin J, et al. Exosome-like nanovesicles derived from Phellinus linteus inhibit Mical2 expression through cross-kingdom regulation and inhibit ultraviolet-induced skin aging. J Nanobiotechnol 2022; 20: 455. PMC9587628 36271377
  57. [66]Duan M Zhang Y Zhang H, et al. Epidermal stem cell-derived exosomes promote skin regeneration by downregulating transforming growth factor-beta1 in wound healing. Stem Cell Res Ther 2020; 11: 452. 33097078 PMC7584097
  58. [67]Wang T Jian Z Baskys A, et al. MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system. Biomaterials 2020; 257: 120264. 32791387
  59. [69]Zhang R Zhu Y Li Y, et al. Human umbilical cord mesenchymal stem cell exosomes alleviate sepsis-associated acute kidney injury via regulating microRNA-146b expression. Biotechnol Lett 2020; 42: 669– 679. 32048128
  60. [70]Songkiatisak P Rahman SMT Aqdas M, et al. NF-kappaB, a culprit of both inflamm-ageing and declining immunity? Immun Ageing 2022; 19: 20. 35581646 PMC9112493
  61. [71]Yasuda S Horinaka M Iizumi Y, et al. Oridonin inhibits SASP by blocking p38 and NF-κB pathways in senescent cells. Biochem Biophys Res Commun 2022; 590: 55– 62. 34971958
  62. [73]Prinelli A Silva-Almeida C Parks S, et al. In-plate cryopreservation of 2D and 3D cell models: Innovative tools for biomedical research and preclinical drug discovery. SLAS Discov 2021; 26: 32– 43. 33021863
  63. [74]Gilliver SC Ruckshanthi JP Atkinson SJ, et al. Androgens influence expression of matrix proteins and proteolytic factors during cutaneous wound healing. Lab Invest 2007; 87: 871– 881. 17607299
  64. [75]St-Jacques B Dassule H Karavanova I, et al. Sonic hedgehog signaling is essential for hair development. Curr Biol 1998; 8: 1058– 1069. 9768360
  65. [76]Kulessa H Turk G Hogan BL. Inhibition of Bmp signaling affects growth and differentiation in the anagen hair follicle. EMBO J 2000; 19: 6664– 6674. 11118201 PMC305899

Cited by

Sorted by citations

Authors
Kim, M.-J., Ahn, H.-J., Kong, D., Lee, S., Kim, D.-H., & Kang, K.-S.
Affiliations
  • Adult Stem Cell Research Center and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
  • Cytotherapy R&D Center, PRIMORIS THERAPEUTICS CO., LTD., Gwangmyeong-si, Gyeonggi-do, Republic of Korea
  • Seoul National University (KR)
  • Kangstem Biotech Co., Ltd. (South Korea) (KR)
Corresponding author
Kang, Kyung-Sun
Venue
Journal of Tissue Engineering
Published
2024-01
Volume
15
Pages
20417314241248753-20417314241248753
ISSN
2041-7314 (ISSN-L)
OpenAlex
W4396724739
Cited by
25
References
11
Citations by year
2026: 10 · 2025: 13 · 2024: 2
FWCI
11.79
Type
journal article
Language
en
Open access
Locations
  • Journal of Tissue Engineering (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministry of Science and ICT, South Korea (23A0101L1)
Topics
  • Health Sciences › Medicine › Urology › Hair Growth and Disorders
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Keywords
photodamage, hair follicle, skin organoids, skin barrier disruption, extracellular matrix degradation, inflammation, exosomes, mesenchymal stem cells, umbilical cord blood, NF-κB activation, hair follicle regeneration

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