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.
Bibliographical noteFunding Information:
The authors thank Editage ( www.editage.co.kr ) for English language editing. This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute , funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI17C1365 ); the Basic Science Research program (grant number NRF-2017R1C1B5017842 ); and the Small Grant for Exploratory Research (SGER) Program (grant numbers NRF-2017R1D1A1A02018088 , -2017R1D1A1A02019212 ) through the National Research Foundation of Korea, funded by the Korean government (Ministry of Education) .
All Science Journal Classification (ASJC) codes
- Cancer Research