3D Co-Culture Model of Endothelial Colony Forming Cells Reverses Late Passage Adipose-Derived Stem Cell Senescence for Wound Healing

The study demonstrated that a 3D co-culture model using endothelial colony forming cells (ECFCs) and late-passage adipose-derived stem cells (ASCs) in a hyaluronic acid gel substrate successfully reversed ASC senescence and restored their morphology, phenotype, secretory profile, and differentiation capacity. The co-culture increased cytokine secretion, such as hepatocyte growth factor, compared to single cell cultures. In a mouse model of chronic injury, wounds treated with ASC/ECFC 3D co-cultures showed improved healing and epithelialization compared to those treated with ASCs or ECFCs alone. The transplanted spheroids exhibited enhanced angiogenic potential, attributed to the transdifferentiation of ASCs into pericytes, indicating a promising therapeutic approach for wound healing.