{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:27:59Z","timestamp":1778873279564,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["2022R1G1A1008848"],"award-info":[{"award-number":["2022R1G1A1008848"]}]},{"name":"EVERBIO","award":["2022R1G1A1008848"],"award-info":[{"award-number":["2022R1G1A1008848"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Androgenetic alopecia suppresses hair follicle growth. This occurs via dihydrotestosterone (DHT), which inhibits key molecular pathways such as Wnt\/\u03b2-catenin and Sonic Hedgehog (SHH) signaling. Exosomes derived from plant callus cultures are promising biomaterials for targeted delivery and regenerative medicine. This study aimed to investigate the protective effects of hemp seed callus-derived exosomes (E40) against DHT-induced inhibition of feather follicle development in a chicken embryo model. Methods: E40 exosomes were isolated and purified from the calli of germinated hemp seeds. A DHT-induced feather loss model was established by injecting chicken embryos on embryonic day 7 (E7) with DHT (50 ng\/mL), with or without co-administration of E40 (40 \u00b5g\/mL). On embryonic day 12 (E12), feather length, density, and expression of molecular markers were analyzed. The methods included FISH, Western blotting, and quantitative analysis of PTCH1, AR, SHH, SMO, GLI1, Wnt, \u03b2-catenin, BMP4, and Noggin. Results: DHT treatment significantly reduced feather length and density. It also downregulated SHH and Wnt\/\u03b2-catenin markers, upregulating BMP4 and androgen receptor expression. Co-treatment with E40 restored feather length and density to levels comparable to controls and significantly recovered the expression of SHH, SMO, GLI1, Wnt, and \u03b2-catenin. E40 also suppressed DHT-induced BMP4 upregulation by approximately 30% and reduced androgen receptor expression. Conclusions: These results suggest that hemp seed-derived exosomes (E40) effectively mitigate DHT-induced feather follicle inhibition by modulating critical signaling pathways and immune-related markers, supporting their potential application as a nanocarrier-based therapeutic strategy for alopecia management.<\/jats:p>","DOI":"10.3390\/ph18081192","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T09:43:01Z","timestamp":1755078181000},"page":"1192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hemp Seed-Derived Exosomes Protect Against Dihydrotestosterone-Induced Chicken Feather Growth Inhibition"],"prefix":"10.3390","volume":"18","author":[{"given":"Hwapyung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Plant Medicals, Gyeongkuk National University, Andong 36729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwangpyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Gyeongkuk National University, Andong 36729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1949-1084","authenticated-orcid":false,"given":"Namsoo Peter","family":"Kim","sequence":"additional","affiliation":[{"name":"VIZO Investment, Washington, DC 20001, USA"},{"name":"VIZO Materials Convergence Foundation, Andong 36729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4029-3824","authenticated-orcid":false,"given":"Boyong","family":"Kim","sequence":"additional","affiliation":[{"name":"VIZO Materials Convergence Foundation, Andong 36729, Republic of Korea"},{"name":"EVERBIO, 131, Jukhyeon-gil, Gwanghyewon-myeon, Jincheon-gun 27809, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12020-017-1280-y","article-title":"Androgenetic alopecia: A review","volume":"57","author":"Lolli","year":"2017","journal-title":"Endocrine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000095251","article-title":"Effect of 5\u03b1-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells","volume":"19","author":"Winiarska","year":"2006","journal-title":"Ski. Pharmacol. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-0625.2004.00255.x","article-title":"Androgen action on human skin\u2013from basic research to clinical significance","volume":"13","author":"Zouboulis","year":"2004","journal-title":"Exp. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1677\/joe.0.1560059","article-title":"Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp","volume":"156","author":"Hibberts","year":"1998","journal-title":"J. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S0190-9622(98)70007-6","article-title":"Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group","volume":"39","author":"Kd","year":"1998","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1046\/j.1523-1747.2003.12174.x","article-title":"Identification of androgen-inducible TGF-\u03b21 derived from dermal papilla cells as a key mediator in androgenetic alopecia","volume":"8","author":"Inui","year":"2003","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"18","DOI":"10.4103\/ijt.ijt_34_22","article-title":"Hair regrowth with novel hemp extract: A case series","volume":"15","author":"Smith","year":"2023","journal-title":"Int. J. Trichol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, D., Kim, N.P., and Kim, B. (2024). Effects of Biomaterials Derived from Germinated Hemp Seeds on Stressed Hair Stem Cells and Immune Cells. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202406.0506.v1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9042345","DOI":"10.1155\/2022\/9042345","article-title":"Exosomes derived from dermal papilla cells mediate hair follicle stem cell proliferation through the Wnt3a\/\u03b2-catenin signaling pathway","volume":"2022","author":"Li","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_10","first-page":"7471246","article-title":"Exosomes secreted from adipose-derived stem cells are a potential treatment agent for immune-mediated alopecia","volume":"2022","author":"Li","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shang, Y., Li, M., Zhang, L., Han, C., Shen, K., Wang, K., Li, Y., Zhang, Y., Luo, L., and Jia, Y. (2024). Exosomes derived from mouse vibrissa dermal papilla cells promote hair follicle regeneration during wound healing by activating Wnt\/\u03b2-catenin signaling pathway. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02689-w"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.chom.2018.10.001","article-title":"Plant-derived exosomal microRNAs shape the gut microbiota","volume":"24","author":"Teng","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/dbio.1998.9103","article-title":"Essential Role forSonic hedgehogduring hair follicle morphogenesis","volume":"205","author":"Chiang","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/S0960-9822(98)70443-9","article-title":"Sonic hedgehog signaling is essential for hair development","volume":"8","author":"Dassule","year":"1998","journal-title":"Curr. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Choi, B.Y. (2020). Targeting Wnt\/\u03b2-catenin pathway for developing therapies for hair loss. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144915"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature06457","article-title":"Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration","volume":"451","author":"Plikus","year":"2008","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.ceb.2006.10.009","article-title":"Molecular signaling in feather morphogenesis","volume":"18","author":"Lin","year":"2006","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/jez.10157","article-title":"Shh-Bmp2 signaling module and the evolutionary origin and diversification of feathers","volume":"294","author":"Harris","year":"2002","journal-title":"J. Exp. Zool."},{"key":"ref_19","first-page":"33","article-title":"Pattern formation in skin development","volume":"34","author":"Sengel","year":"1990","journal-title":"Int. J. Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1080\/00071668.2020.1758302","article-title":"Investigation of feather follicle morphogenesis and the expression of the Wnt\/\u03b2-catenin signaling pathway in yellow-feathered broiler chick embryos","volume":"61","author":"Xie","year":"2020","journal-title":"Br. Poult. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1093\/ps\/86.10.2059","article-title":"Functional genomics of the chicken\u2014A model organism","volume":"86","author":"Cogburn","year":"2007","journal-title":"Poult. Sci."},{"key":"ref_22","unstructured":"Institute of Laboratory Animal Resources (US) (1986). Committee on Care, Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals, US Department of Health and Human Services, Public Health Service, National Institutes of Health."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1104\/pp.16.01253","article-title":"Extracellular vesicles isolated from the leaf apoplast carry stress-response proteins","volume":"173","author":"Rutter","year":"2017","journal-title":"Plant Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1016\/j.febslet.2009.09.041","article-title":"Vesicular fractions of sunflower apoplastic fluids are associated with potential exosome marker proteins","volume":"583","author":"Regente","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Liu, Y., Liu, H., and Tang, W. (2019). Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci., 9.","DOI":"10.1186\/s13578-019-0282-2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/exd.13927","article-title":"Exosomes derived from human dermal papilla cells promote hair growth in cultured human hair follicles and augment the hair-inductive capacity of cultured dermal papilla spheres","volume":"28","author":"Kwack","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kazi, T., Nagata, A., Nakagawa, T., Matsuzaki, T., and Inui, S. (2022). Dermal papilla cell-derived extracellular vesicles increase hair inductive gene expression in adipose stem cells via \u03b2-catenin activation. Cells, 11.","DOI":"10.3390\/cells11020202"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13287-024-03906-x","article-title":"Improvement of androgenic alopecia by extracellular vesicles secreted from hyaluronic acid-stimulated induced mesenchymal stem cells","volume":"15","author":"Oh","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/ijd.17406","article-title":"The efficacy of adipose stem cell-derived exosomes in hair regeneration based on a preclinical and clinical study","volume":"63","author":"Lee","year":"2024","journal-title":"Int. J. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/exd.13909","article-title":"A multiscale hybrid mathematical model of epidermal-dermal interactions during skin wound healing","volume":"28","author":"Wang","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1152\/physrev.2001.81.1.449","article-title":"Controls of hair follicle cycling","volume":"81","author":"Stenn","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kim, H., and Kim, B. (2024). Osteogenic Protection against Fine Dust with Erucic Acid-Induced Exosomes. J. Funct. Biomater., 15.","DOI":"10.3390\/jfb15080215"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1192\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:26:12Z","timestamp":1760034372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ph18081192"],"URL":"https:\/\/doi.org\/10.3390\/ph18081192","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]}}}