Targeting macrophage polarization: mechanisms and potential of mesenchymal stromal/stem cells therapy in acne treatment- a narrative review.

Acne vulgaris(AV) is a clinically common skin disease. Globally, about one in ten individuals is affected by it. Current research on acne primarily focuses on the following four areas: first, the inflammatory response; second, sebum metabolism disorders; third, the colonization of Cutibacterium acnes (C. acnes); and fourth, abnormal keratinization of the pilosebaceous duct. Although the exact pathogenesis of this condition has not yet been fully elucidated, the dual polarization of macrophages play a crucial role in the onset, progression and outcome of acne. As key effector cells in the human immune system, macrophages can exhibit different phenotypes in the microenvironments of various diseases: the classical activated phenotype (M1), the alternative activated phenotype (M2), and a subset characterized by the expression of trigger receptor 2 (TREM2) in myeloid cells. Currently endorsed international acne therapy, encompassing topical agents, systemic drugs, and physical therapies, demonstrates efficacy but frequently elicits a range of adverse effects. Therefore, there is a pressing need for a new, ideal treatment approach. Extensive research on stem cells and their derivatives in recent years has shown that mesenchymal stromal/stem cells (MSCs) possess significant immunomodulatory and anti-inflammatory capabilities, particularly in terms of influencing macrophage polarization. They promote the transition of macrophages to the anti-inflammatory M2 phenotype, which may play a role in the recovery process of acne. The unique advantage of MSCs therapy is that it is not simply antibacterial or anti-inflammatory as traditional therapies; rather, it may alleviate inflammation and promote skin tissue repair by promoting polarization of M2 macrophages. At the same time, it is expected to avoid the common adverse reactions in current acne treatment methods. This paper aims to provide a narrative review on the function of macrophages in skin tissue, the core role of inflammatory responses in acne pathogenesis, the multifaceted functions of macrophages in acne, the mechanisms through which MSCs regulate macrophage polarization, the current guideline-recommended standard treatment protocols for acne, and the feasibility of MSCs and their derivative transplants as a therapeutic strategy for alleviating acne inflammation.