{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:10:10Z","timestamp":1789549810842,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background\/Objectives: Hair loss affects self-esteem, confidence, and psychological well-being. Exosomes, as molecular carriers of growth factors and active compounds, offer a promising treatment. This study evaluates the efficacy of an exosome formulation containing extracts from two known hair-regenerating plants, Ecklonia cava and Thuja orientalis (ECPE), for male pattern alopecia. Methods: A randomized controlled trial included 20 male participants with Norwood grade 2\u20133 androgenetic alopecia who were randomly assigned into two groups, placebo (0.9% sodium chloride) and ECPE, administered bi-weekly across four sessions. Evaluations included hair density measurements, adverse effect tracking, and self-assessments. Results: Most participants (55%) were aged 18 to 35, with 75% reporting hair loss for over a year and 80% noting scalp thinning. The hair counts showed no significant change in the placebo group from baseline to week 16 (Wilcoxon signed-rank test: V = 13.5, p = 0.163), while a significant increase was observed in the ECPE group (V = 0, p = 0.002). Between-group analysis revealed a significant difference in the hair count changes (Wilcoxon rank-sum test: W = 86.5, p = 0.006) with a large effect size (Cliff\u2019s Delta: &amp; = 0.73, 95% CI: 0.41\u20130.89), with the ECPE group showing higher median hair growth (9.5, IQR = 16.88) compared to the placebo group (1.5, IQR = 3.00). A Bayesian ANCOVA, adjusted for covariates (the father\u2019s scalp hair condition, baseline hair count, and Norwood classification), showed no significant effect of these factors on the outcomes. Conclusions: These findings suggest that ECPE significantly improves hair regrowth compared to the placebo, with no notable adverse effects.<\/jats:p>","DOI":"10.3390\/life15030500","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T07:59:54Z","timestamp":1742457594000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A Pilot Randomized Controlled Trial (RCT) Evaluating the Efficacy of an Exosome-Containing Plant Extract Formulation for Treating Male Alopecia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-0851","authenticated-orcid":false,"given":"Farahnaz","family":"Amini","sequence":"first","affiliation":[{"name":"Faculty of Medicine (Neurology), University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Ju","family":"Teh","sequence":"additional","affiliation":[{"name":"School of Healthy Ageing, Aesthetics & Regenerative Medicine, Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-2217","authenticated-orcid":false,"given":"Chung Keat","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Healthy Ageing, Aesthetics & Regenerative Medicine, Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5711-4808","authenticated-orcid":false,"given":"Eugenie Sin Sing","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Healthy Ageing, Aesthetics & Regenerative Medicine, Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9077-5894","authenticated-orcid":false,"given":"Edmond Siah Chye","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Healthy Ageing, Aesthetics & Regenerative Medicine, Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mao, M.-Q., Jing, J., Miao, Y.-J., and Lv, Z.-F. (2022). Epithelial-Mesenchymal Interaction in Hair Regeneration and Skin Wound Healing. Front. Med., 9.","DOI":"10.3389\/fmed.2022.863786"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s12967-021-02980-6","article-title":"A Paradigm Shift in Cell-Free Approach: The Emerging Role of MSCs-Derived Exosomes in Regenerative Medicine","volume":"19","author":"Moghadasi","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Cho, B.S., Lee, J., Won, Y., Duncan, D.I., Jin, R.C., Lee, J., Kwon, H.H., Park, G.-H., Yang, S.H., and Park, B.C. (2020). Skin Brightening Efficacy of Exosomes Derived from Human Adipose Tissue-Derived Stem\/Stromal Cells: A Prospective, Split-Face, Randomized Placebo-Controlled Study. Cosmetics, 7.","DOI":"10.3390\/cosmetics7040090"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1111\/jocd.15869","article-title":"Systematic Review of Exosome Treatment in Hair Restoration: Preliminary Evidence, Safety, and Future Directions","volume":"22","author":"Gupta","year":"2023","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/cbin.12099","article-title":"Exosomes Derived from uMSCs Promote Hair Regrowth in Alopecia Areata through Accelerating Human Hair Follicular Keratinocyte Proliferation and Migration","volume":"48","author":"Hu","year":"2024","journal-title":"Cell Biol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/jocd.14153","article-title":"Exosomes Derived from Human Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Dupilumab-Related Facial Redness in Patients with Atopic Dermatitis: A Report of Two Cases","volume":"21","author":"Park","year":"2022","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s40883-021-00204-3","article-title":"Exploring the Potential of Mesenchymal Stem Cell\u2013Derived Exosomes for the Treatment of Alopecia","volume":"7","author":"Ajit","year":"2021","journal-title":"Regen. Eng. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.molimm.2021.02.021","article-title":"Dermal Macrophage and Its Potential in Inducing Hair Follicle Regeneration","volume":"134","author":"Gao","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.4103\/tjo.tjo_9_21","article-title":"Retinal Artery Occlusion Following Cosmetic Injection of Poly-L-Lactic Acid","volume":"11","author":"Wu","year":"2021","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.bbrc.2018.04.067","article-title":"Regulation of Hair Follicle Development by Exosomes Derived from Dermal Papilla Cells","volume":"500","author":"Zhou","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6407","DOI":"10.3390\/ijms13056407","article-title":"Effect of Dieckol, a Component of Ecklonia Cava, on the Promotion of Hair Growth","volume":"13","author":"Kang","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Park, S., and Lee, J. (2021). Modulation of Hair Growth Promoting Effect by Natural Products. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122163"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.5021\/ad.2016.28.1.15","article-title":"Enhancement of Human Hair Growth Using Ecklonia Cava Polyphenols","volume":"28","author":"Shin","year":"2016","journal-title":"Ann. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, N., Park, D.K., and Park, H.-J. (2013). Hair Growth-Promoting Activity of Hot Water Extract of Thuja Orientalis. BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-9"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1177\/0962280215588241","article-title":"Estimating the Sample Size for a Pilot Randomised Trial to Minimise the Overall Trial Sample Size for the External Pilot and Main Trial for a Continuous Outcome Variable","volume":"25","author":"Whitehead","year":"2016","journal-title":"Stat. Methods Med. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1111\/jocd.14537","article-title":"Treatment Options for Androgenetic Alopecia: Efficacy, Side Effects, Compliance, Financial Considerations, and Ethics","volume":"20","author":"Nestor","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Delamere, F.M., Sladden, M.J., Dobbins, H.M., and Leonardi-Bee, J. (2008). Interventions for Alopecia Areata. Cochrane Database Syst. Rev., CD004413.","DOI":"10.1002\/14651858.CD004413.pub2"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1007\/s00266-022-03224-8","article-title":"Platelet-Rich Plasma for Treatment of Hair Loss Improves Patient-Reported Quality of Life","volume":"47","author":"Meyers","year":"2023","journal-title":"Aesth Plast. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13287-023-03440-2","article-title":"Combination of Adipose-Derived Stem Cell Conditioned Media and Minoxidil for Hair Regrowth in Male Androgenetic Alopecia: A Randomized, Double-Blind Clinical Trial","volume":"14","author":"Legiawati","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s13770-020-00266-4","article-title":"Human Hair Outer Root Sheath Cells and Platelet-Lysis Exosomes Promote Hair Inductivity of Dermal Papilla Cell","volume":"17","author":"Nilforoushzadeh","year":"2020","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1111\/jocd.16261","article-title":"Hair Repigmentation of Poliosis Circumscripta in Androgenetic Alopecia Patient Treated with Exosomes and Fractional Picosecond Laser","volume":"23","author":"Lueangarun","year":"2024","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2174\/1574888X12666170522114307","article-title":"Hair Regeneration Therapy: Application of Adipose-Derived Stem Cells","volume":"12","author":"Fukuoka","year":"2017","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"273","DOI":"10.5992\/AJCS-D-12-00015.1","article-title":"The Latest Advance in Hair Regeneration Therapy Using Proteins Secreted by Adipose-Derived Stem Cells","volume":"29","author":"Fukuoka","year":"2012","journal-title":"Am. J. Cosmet. Surg."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/3\/500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:57:04Z","timestamp":1760029024000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/3\/500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["life15030500"],"URL":"https:\/\/doi.org\/10.3390\/life15030500","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,20]]}}}