{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T18:53:45Z","timestamp":1779130425088,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T00:00:00Z","timestamp":1707004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1F1A1060052"],"award-info":[{"award-number":["2021R1F1A1060052"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Limited evidence suggests that stimulating adipose-derived stem cells (ASCs) indirectly promotes hair growth. We examined whether bee venom (BV) activated ASCs and whether BV-induced hair growth was facilitated by enhanced growth factor release by ASCs. The induction of the telogen-to-anagen phase was studied in mice. The underlying mechanism was investigated using organ cultures of mouse vibrissa hair follicles. When BV-treated ASCs were injected subcutaneously into mice, the telogen-to-anagen transition was accelerated and, by day 14, the hair weight increased. Quantitative polymerase chain reaction (qPCR) revealed that BV influenced the expression of several molecules, including growth factors, chemokines, channels, transcription factors, and enzymes. Western blot analysis was employed to verify the protein expression levels of extracellular-signal-regulated kinase (ERK) and phospho-ERK. Both the Boyden chamber experiment and scratch assay confirmed the upregulation of cell migration by BV. Additionally, ASCs secreted higher levels of growth factors after exposure to BV. Following BV therapy, the gene expression levels of alkaline phosphatase (ALP), fibroblast growth factor (FGF)-1 and 6, endothelial cell growth factor, and platelet-derived growth factor (PDGF)-C were upregulated. The findings of this study suggest that bee venom can potentially be utilized as an ASC-preconditioning agent for hair regeneration.<\/jats:p>","DOI":"10.3390\/toxins16020084","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T07:50:12Z","timestamp":1707205812000},"page":"84","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bee Venom Stimulates Growth Factor Release from Adipose-Derived Stem Cells to Promote Hair Growth"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-1348","authenticated-orcid":false,"given":"Jung Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul 05278, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Traditional Korean Medicine Practice, Jaseng Medical Foundation, 538, Gangnam-daero, Gangnam-gu, Seoul 06110, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4287-2264","authenticated-orcid":false,"given":"Bonhyuk","family":"Goo","sequence":"additional","affiliation":[{"name":"Department of Acupuncture & Moxibustion, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul 05278, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeoncheol","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Acupuncture & Moxibustion Medicine, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, 26, Kyungheedae-ro 4-gil, Dongdaemun-gu, Seoul 02453, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41392-020-00441-y","article-title":"Functional hair follicle regeneration: An updated review","volume":"6","author":"Ji","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"dev198671","DOI":"10.1242\/dev.198671","article-title":"Cyclic growth of dermal papilla and regeneration of follicular mesenchymal components during feather cycling","volume":"148","author":"Wu","year":"2021","journal-title":"Development"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Choi, N., Shin, S., Song, S.U., and Sung, J.-H. (2018). Minoxidil promotes hair growth through stimulation of growth factor release from adipose-derived stem cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030691"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.jaad.2017.09.011","article-title":"Alopecia areata is a medical disease","volume":"78","author":"Korta","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000492035","article-title":"Complementary and alternative treatments for alopecia: A comprehensive review","volume":"5","author":"Hosking","year":"2019","journal-title":"Ski. Appendage Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s40257-018-0387-0","article-title":"Efficacy of topical combination of 0.25% finasteride and 3% minoxidil versus 3% minoxidil solution in female pattern hair loss: A randomized, double-blind, controlled study","volume":"20","author":"Suchonwanit","year":"2019","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sung, S.-H., Kim, J.-W., Han, J.-E., Shin, B.-C., Park, J.-K., and Lee, G. (2021). Animal venom for medical usage in pharmacopuncture in Korean medicine: Current status and clinical implication. Toxins, 13.","DOI":"10.3390\/toxins13020105"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bava, R., Castagna, F., Musella, V., Lupia, C., Palma, E., and Britti, D. (2023). Therapeutic use of bee venom and potential applications in veterinary medicine. Vet. Sci., 10.","DOI":"10.3390\/vetsci10020119"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gu, H., Han, S.M., and Park, K.-K. (2020). Therapeutic effects of apamin as a bee venom component for non-neoplastic disease. Toxins, 12.","DOI":"10.3390\/toxins12030195"},{"key":"ref_10","first-page":"576","article-title":"Effects of adipose-derived stem cells and platelet-rich plasma exosomes on the inductivity of hair dermal papilla cells","volume":"23","author":"Nilforoushzadeh","year":"2021","journal-title":"Cell J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s13770-021-00347-y","article-title":"Adipose-derived stem cell exosomes promoted hair regeneration","volume":"18","author":"Wu","year":"2021","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1089\/scd.2013.0460","article-title":"The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells","volume":"23","author":"Kim","year":"2014","journal-title":"Stem Cells Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jdermsci.2009.10.013","article-title":"Hair growth promoting effects of adipose tissue-derived stem cells","volume":"57","author":"Won","year":"2010","journal-title":"J. Dermatol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41536-017-0013-4","article-title":"Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal","volume":"2","author":"Moffatt","year":"2017","journal-title":"NPJ Regen. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/1523-1747.ep12326964","article-title":"Vascular endothelial growth factor is an autocrine growth factor for hair dermal papilla cells","volume":"106","author":"Lachgar","year":"1996","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lin, W.H., Xiang, L.J., Shi, H.X., Zhang, J., Jiang, L.P., Cai, P.T., Lin, Z.L., Lin, B.B., Huang, Y., and Zhang, H.L. (2015). Fibroblast growth factors stimulate hair growth through \u03b2-catenin and Shh expression in C57BL\/6 mice. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/730139"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lee, S.-H., Yoon, J., Shin, S.H., Zahoor, M., Kim, H.J., Park, P.J., Park, W.-S., Min, D.S., Kim, H.-Y., and Choi, K.-Y. (2012). Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034152"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1248\/bpb.b16-00158","article-title":"Bee venom promotes hair growth in association with inhibiting 5\u03b1-reductase expression","volume":"39","author":"Park","year":"2016","journal-title":"Biol. Pharm. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.toxicon.2008.06.007","article-title":"Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells","volume":"52","author":"Tu","year":"2008","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.cell.2011.07.019","article-title":"Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling","volume":"146","author":"Festa","year":"2011","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1126\/science.1180794","article-title":"Coexistence of quiescent and active adult stem cells in mammals","volume":"327","author":"Li","year":"2010","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3892\/mmr.2013.1796","article-title":"Differentiation of human hair follicle stem cells into endothelial cells induced by vascular endothelial and basic fibroblast growth factors","volume":"9","author":"Xu","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/ics.12489","article-title":"Review of hair follicle dermal papilla cells as in vitro screening model for hair growth","volume":"40","author":"Madaan","year":"2018","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1126\/science.aar4800","article-title":"Endothelial cell adaptation in regeneration","volume":"362","author":"Rafii","year":"2018","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cell.2010.11.049","article-title":"Dynamics between stem cells, niche, and progeny in the hair follicle","volume":"144","author":"Hsu","year":"2011","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/1357-4310(96)10045-9","article-title":"Growth factors and cytokines in hair follicle development and cycling: Recent insights from animal models and the potentials for clinical therapy","volume":"2","author":"Danilenko","year":"1996","journal-title":"Mol. Med. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/j.0022-202X.2005.23693.x","article-title":"Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles","volume":"124","author":"Kawano","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rendl, M., Lewis, L., and Fuchs, E. (2005). Molecular dissection of mesenchymal\u2013epithelial interactions in the hair follicle. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030331"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1677\/joe.0.1560543","article-title":"Deceleration by angiotensin II of the differentiation and bone formation of rat calvarial osteoblastic cells","volume":"156","author":"Hagiwara","year":"1998","journal-title":"J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jdermsci.2011.01.013","article-title":"Minoxidil activates \u03b2-catenin pathway in human dermal papilla cells: A possible explanation for its anagen prolongation effect","volume":"62","author":"Kwack","year":"2011","journal-title":"J. Dermatol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13287-017-0568-4","article-title":"ERK signaling is required for VEGF-A\/VEGFR2-induced differentiation of porcine adipose-derived mesenchymal stem cells into endothelial cells","volume":"8","author":"Almalki","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/pin.12924","article-title":"S100A12 promotes inflammation and apoptosis in ischemia\/reperfusion injury via ERK signaling in vitro study using PC12 cells","volume":"70","author":"Zhang","year":"2020","journal-title":"Pathol. Int."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/2\/84\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:54:53Z","timestamp":1760104493000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/2\/84"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,4]]},"references-count":33,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["toxins16020084"],"URL":"https:\/\/doi.org\/10.3390\/toxins16020084","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,4]]}}}