Hypoxia, Serum Starvation, and TNF-α Can Modify the Immunomodulation Potency of Human Adipose-Derived Stem Cells.

Abstract

Adipose-derived stem cells (ADSCs) are mesenchymal stem cells (MSCs) that are found in adipose tissues, which are easily obtained from liposuction procedures using an enzyme mixture. The adhering cells are then selectively cultivated. ADSCs have great potential in regenerative medicine because they are plentiful, easily accessible, and less invasive. They also have an impressive proliferation ability and can be differentiated into mesenchymal lineages and trans-differentiating into many other cell types. In particular, they have extraordinary abilities in immunomodulation. This study aimed to investigate the effects of culture conditions (hypoxia, starvation, and TNF-α treatment) on the immunomodulation of human ADSCs. Human ADSCs were expanded in vitro in the standard condition before they were cultured in different stress conditions. ADSCs from passages fifth were confirmed as MSCs by some standard assays suggested by the International Society for Cell and Gene Therapy. These MSCs were used to culture in four different stress conditions: hypoxia, serum starvation, and TNF-α treatment in 48h. After treatments, MSCs were used to evaluate their immunomodulation capacity using MSCs mixed lymphocyte reaction assay, and the concentrations of IDO, PGE2, IL-6, and IL-10 were secreted in the culture medium. In different stress conditions, ADSCs exhibited different responses related to their immunomodulation. In serum starvation, ADSCs exerted a strong secretion of IDO and PGE2, whereas they showed strong IL-6 secretion in the TNF-α-supplemented medium. When exposed to lymphocytes, ADSCs caused an increase in the ratio of regulatory T cells (Tregs), and co-culture lymphocytes with ADSCs induced in hypoxic malnutrition conditions increased the IL-10 level the most. In addition, when exposed to dendritic cells (DCs), ADSCs inhibited the mature marker expressions of the DCs. The current research showed that ADSCs change their immunomodulation properties to survive in in vitro culture environments. Treatment of ADSCs in the starvation medium for 48h can increase the immunomodulation of ADSCs.