Abstract

Although mesenchymal stem cells (MSCs) have been reported to inhibit tumor growth, the mechanism controlling this tumor suppression function is unclear. Here, we report that high-density (40,000 cells/cm²) cultured adipose tissue-derived MSCs (40K-ASCs) expressed interferon (IFN)-β and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); we also found that serum deprivation during cell culture induced the expression of IFN-β and TRAIL. In addition, the mRNA expression of IFN-β, but not TRAIL, was increased during the washing step required for the transplantation of normal-density (5000 cells/cm²) cultured ASCs (5K-ASCs). When the human lung cancer cell line H460 was co-cultured with 40K-ASCs, necrotic cell death was dramatically increased in vitro. When ASCs were injected after four washes, both 5K-ASCs and 40K-ASCs substantially reduced tumor weight in H460-derived cancer animal models. These results suggest that serum deprivation during the culture of 40K-ASCs or during the washing step of 5K-ASCs can induce IFN-β and/or TRAIL expression, ultimately leading to the tumor suppression capability of ASCs.