Exploring Circadian Oscillation in Human Umbilical Cord–Derived Mesenchymal Stem Cells During Passaging

Objective: Circadian clock genes regulate key cellular functions and regenerative medicine; however, their role in human umbilical cord–derived mesenchymal stem cells (hUC-MSCs) remains unclear.Methods: We analyzed the expression of core circadian genes (CLOCK, BMAL1, PER1, PER2, PER3, CRY1, and REV-ERBα) in hUC tissues and isolated hUC-MSCs over 48 hours at 6-hour intervals. The effects of cell confluence and passage number on gene expression, proliferation, and migration were evaluated.Results: Circadian clock genes were actively expressed in both hUC tissues and hUC-MSCs, indicating an intrinsic circadian regulatory mechanism. Several genes exhibited low-amplitude circadian oscillations. Notably, expression levels were significantly higher at high cell confluence, suggesting a role in cell proliferation and intercellular communication. Early-passage hUC-MSCs demonstrated superior proliferation and migration capacities compared to late-passage cells, highlighting their enhanced regenerative potential.Conclusion: Circadian clock genes influence hUC-MSC function, with early-passage cells demonstrating superior regenerative potential. These findings highlight the importance of passage-dependent circadian regulation in optimizing hUC-MSCs for therapeutic applications.