Importance of the origin of mesenchymal (stem) stromal cells in cancer biology: “alliance” or “war” in intercellular signals

Mesenchymal stem cells (MSCs) play a central role in the intercellular signaling within the tumor microenvironment (TME), exchanging signals with cancer cells and tumor stromal cells, such as cancer-associated fibroblasts and inflammatory mononuclear cells. Research attributes both pro-tumor and anti-tumor actions to MSCs; however, evidence indicates that MSCs specific effect on the tumor depends on the source of the MSCs and the type of tumor. There are consistent data proving that MSCs from reproductive tissues, such as the uterus, umbilical cord or placenta, have potent anti-tumor effects and tropism towards tumor tissues. More interestingly, products derived from MSCs, such as secretome or extracellular vesicles, seem to reproduce the effects of their parental cells, showing a potential advantage for clinical treatments by avoiding the drawbacks associated with cell therapy. Given these perspectives, it appears necessary new research to optimize the production, safety and antitumor potency of the products derived from the MSCs suitable for oncological therapies.