Decoding Sebaceous Gland Biology Through Experimental Models: Progress, Limitations, and Future Directions.

The sebaceous gland (SG) is a highly dynamic skin appendage that plays a central role in maintaining skin homeostasis through lipid production, immune modulation, and interactions with the skin microbiome. Dysregulation of SG function is implicated in several dermatological disorders, including acne and other inflammatory skin diseases. Over the past decades, a wide range of experimental models has been developed to investigate SG biology and pathology. These include in vivo animal models, ex vivo human skin explants, primary sebocyte cultures, and immortalized sebocyte cell lines, each offering distinct advantages and limitations. More recently, significant progress has been made in the development of advanced three-dimensional (3D) models of sebaceous gland biology, including sebocyte spheroids, SG organoids, human skin equivalents containing sebaceous components, and organotypic co-culture models, which better recapitulate the structural and functional complexity of SGs. In particular, the emergence of SG organoids derived from adult or pluripotent stem cells represents a breakthrough, enabling the study of sebocyte differentiation, lipid metabolism, and cell-cell interactions in a physiologically relevant context. Despite these advances, current models still face important challenges, including incomplete cellular maturation, limited representation of the immune and vascular components, and insufficient modeling of the native skin microenvironment. Future developments integrating bioengineering approaches, microfluidic platforms, and multi-cellular systems are expected to further enhance model complexity and translational relevance. This review summarizes current knowledge on experimental models developed to study SG and sebocyte physiology and pathology.