Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 20 3 2026 09 29 336 351 Wahyu Widowati 1) Department of Pharmacology, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia 2) Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia Hendy Pratama Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia Medissia Patricia Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia Pieter Raja Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia Putu Irmayani Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia Clarissa Suseno Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia Zesven Zesven Master Program of Skin Ageing and Aesthetic Medicine, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia Dwi Triharsiwi Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, Bandung 40163, West Java, Indonesia Van Xuan Faculty of Biological Science, Nong Lam Univeristy of Ho Chi Minh City, Linh Trung Ward, Thu Duc Distric, Ho Chi Minh City, Vietnam Rizky Pratama Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, Bandung 40163, West Java, Indonesia Rizal Azis Biomedical Engineering, Department of Electrical Engineering, Faculty of Engineering, Universitas Indonesia, Depok, Indonesia 2025 08 27 2026 07 26 Hair loss is a commonly encountered condition that often causes significant distress with diverse etiologies, including androgenic, autoimmune, inflammatory, and aging-related mechanisms. Current therapeutic options, such as minoxidil and finasteride, often exhibit limited efficacy and are associated with adverse effects, necessitating the exploration of safer and more effective alternatives. This review aims to explore the therapeutic potential of mesenchymal stem cell (MSC)-derived secretome as a novel cell-free approach for hair restoration. A narrative review of recent preclinical, in vivo, and early clinical studies was conducted to evaluate the role of MSC-secretome components, including growth factors, cytokines, extracellular vesicles, and exosomes, in modulating key pathways involved in the regeneration of hair follicles. In vitro and ex vivo models demonstrate that MSC-secretome enhances the proliferation, migration, and survival of dermal papilla cells and hair follicle stem cells by activation of the Wnt/β-catenin, IGF-1, VEGF, and PI3K/AKT signaling pathways via paracrine signaling. In vivo animal models of alopecia indicate accelerated anagen initiation, follicle reactivation, improved dermal papilla function, and reduced inflammatory mediators following treatment with MSC-conditioned medium or exosomes. Early clinical evidence, including topical MSC-conditioned medium application in alopecia areata, suggests improved follicular density and hair shaft thickness without significant adverse effects. In conclusion, MSC-derived secretome represents a promising, cell-free strategy for hair regeneration. Future research should prioritize optimizing production protocols, standardizing active components, validating potency assays, addressing regulatory and manufacturing challenges, and conducting well-designed clinical trials to ensure consistent therapeutic outcomes. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/2517 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/2517/1146