Stem cell-based therapies for alopecia areata: a narrative review

Abstract

Alopecia Areata (AA) is a chronic inflammatory disorder characterized by non-scarring, patchy hair loss that may progress to the entire scalp (alopecia totalis) or body (alopecia universalis), significantly impairing patients’ quality of life and psychological health. Although the exact pathogenesis of AA remains unclear, current evidence suggests that the breakdown of hair follicle immune privilege (IP) and subsequent autoimmune-mediated follicular attack play a pivotal role. Conventional therapeutic modalities, including corticosteroid and Janus kinase (JAK) inhibitors, are often limited by suboptimal efficacy in severe cases and high relapse rates following treatment cessation. In recent years, stem cell-based therapy has emerged as a novel treatment for AA, showing therapeutic potential through multiple mechanisms. Preliminary clinical trials have indicated significant efficacy in promoting hair regrowth among AA patients. However, comprehensive evaluation of long-term safety and therapeutic efficacy remains imperative. This review article aims to give a comprehensive overview of the recent advances in stem cell-based therapies for AA and explore their underlying mechanisms and clinical application prospects, hoping to provide a framework and reference for future research and clinical practice.

1. Introduction

Alopecia Areata (AA) is a prevalent chronic inflammatory disorder characterized by non-scarring hair loss, characterized by sudden onset and an unpredictable clinical course of spontaneous remission and recurrence. The clinical manifestations of AA range from localized well-defined patches of alopecia to widespread hair loss of the entire scalp (alopecia totalis, AT) or body (alopecia universalis, AU). AA affects people of all genders and ages, with a cumulative lifetime incidence of 2% [1, 2]. Although the disease is not life-threatening, it has a severe psychological impact on the affected individuals, affecting their self-esteem and quality of life [3, 4]. The pathogenesis of AA is not fully understood, with current evidence implicating a multifactorial etiology involving genetic predisposition, immune dysregulation, oxidative stress, microbial factors, and epigenetic modification [5–7]. Treatments for AA include corticosteroids (topical, intralesional, and systemic), immunosuppressive agents (e.g., cyclosporine), contact immunotherapy (e.g. diphenylcyclopropenone (DPCP) and squaric acid dibutylester (SADBE)), minoxidil and Janus kinase (JAK) inhibitors. However, no therapy offers a definitive cure for AA, and side effects and relapse are not uncommon. Therefore, the search for more effective and long-lasting treatment has become an important area of AA research.

Stem cells are a distinct cell population that has the properties of self-renewal and multilineage differentiation. Based on their origin, they can be classified as embryonic, fetal, perinatal, adult stem cells, and induced pluripotent stem cells (iPSC) [8]. Perinatal stem cells are derived from amniotic fluid, placenta, and umbilical cord, while adult stem cells reside in various adult organs/tissues. In regenerative medicine, mesenchymal stem cells (MSCs) are the most utilized stem cells due to their ease of accessibility, low immunogenicity, and potent regenerative properties [9]. These cells are extensively distributed across various human tissues and organs, including bone marrow, adipose tissue, umbilical cord, and menses blood [10]. In addition to direct stem cell transplantation, stem cell-derived conditioned media (CM) and exosomes have emerged as promising cell-free therapeutic strategies in regenerative medicine.