Exploring Morphological and Molecular Properties of Different Adipose Cell Models: Monolayer, Spheroids, Gellan Gum‐Based Hydrogels, and Explants

White adipose tissue (WAT) plays a crucial role in energy homeostasis and secretes numerous adipokines with far-reaching effects. WAT is linked to diseases such as diabetes, cardiovascular disease, and cancer. There is a high demand for suitable in vitro models to study diseases and tissue metabolism. Most of these models are covered by 2D-monolayer cultures. This study aims to evaluate the performance of different WAT models to better derive potential applications. The stability of adipocyte characteristics in spheroids and two 3D gellan gum hydrogels with ex situ lobules and 2D-monolayer culture is analyzed. First, the differentiation to achieve adipocyte-like characteristics is determined. Second, to evaluate the maintenance of differentiated ASC-based models, an adipocyte-based model, and explants over 3 weeks, viability, intracellular lipid content, perilipin A expression, adipokine, and gene expression are analyzed. Several advantages are supported using each of the models. Including, but not limited to, the strong differentiation in 2D-monolayers, the self-assembling within spheroids, the long-term stability of the stem cell-containing hydrogels, and the mature phenotype within adipocyte-containing hydrogels and the lobules. This study highlights the advantages of 3D models due to their more in vivo-like behavior and provides an overview of the different adipose cell models.