Effect of exosomes derived from induced and human adipose tissue-derived mesenchymal stem cells on human cancer cells.

Abstract

Exosomes (Exos) derived from mesenchymal stem cells (MSCs) are known to influence cancer cell behavior; however, the clinical use of MSCs is limited due to the gradual loss of their differentiation potential with continuous passaging. Induced mesenchymal stem cells (iMSCs) have emerged as a promising alternative source, but the effects of Exos derived from iMSCs (iMSC-Exos) on cancer cells remain incompletely understood. This study aims to compare the effects of iMSC-Exos with ADMSC-Exos derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) on the viability, invasion, and migration of breast (MCF7) and lung (A549) cancer cells. Conditioned media from iMSCs and ADMSCs were collected for isolation and characterization of Exos. MCF7 and A549 cell lines were treated with iMSC- and ADMSC-Exos, and Exos uptake, cell viability, migration, senescence, and expression of BAX and BCL-2 genes were evaluated. iMSCand ADMSC-Exos were successfully internalized into cancer cells, with a higher efficiency of ADMSC-Exos uptake in MCF7 cells. Cell viability decreased and migration increased in both cancer cell lines upon treatment. BAX expression was significantly reduced in MCF7 cells following ADMSC-Exos treatment and in A549 cells after iMSC-Exos treatment. In contrast, BCL-2 expression was significantly reduced in MCF7 cells treated with both iMSC- and ADMSC-Exos, while it significantly increased in A549 cells after ADMSC-Exos treatment. A549 lung cancer cells showed a higher level of senescence than MCF7 breast cancer cells, particularly when treated with iMSC-Exos. Minimal overall differences were observed in viability, apoptosis, and migration assays between iMSC- and ADMSC-Exos in MCF7 and A549 cells. However, significant differences were observed in the senescence and expression of BAX and BCL-2 genes across cancer cell lines. These findings highlight the importance of further investigation into the distinct effects of iMSC- and ADMSC-Exos on cancer cell biology.