Small spheroids of adipose-derived stem cells with time-dependent enhancement of IL-8 and VEGF-A secretion.

Wound-healing factors secreted from mesenchymal stem cells (MSCs) modulate the immune response and facilitate proliferation of neighboring cells. Although in vitro three-dimensional (3D) culture techniques have improved the therapeutic potential of MSCs, no studies have focused on the effects of cell aggregation alone. In this study, the effect of cell aggregation on the up-regulation of wound-healing proteins secretions was investigated by constructing small spheroids of human adipose-derived stem cells (hADSCs) on a micropatterned surface. These spheroids were mostly unaffected by the secondary effects of cell aggregation, such as hypoxia, low-nutrient supply, and metabolic waste accumulation. Small spheroids of hADSCs, which were of 100 μm in diameter, were successfully constructed using micropatterned surface. Expression of the wound-healing-related factors, VEGF-A and IL-8, was markedly enhanced at the gene and protein levels, whereas the enhancement of VEGF-A expression was transient and IL-8 enhancement was maintained for a long time.