Stem cell-derived exosomes: roles in stromal remodeling, tumor progression, and cancer immunotherapy

Abstract\ud Stem cells are known to maintain stemness at least in part through secreted factors that promote stem-like phenotypes in resident cells. Accumulating evidence has clarified that stem cells release nano-vesicles, known as exosomes, which may serve as mediators of cell-to-cell communication and may potentially transmit stem cell phenotypes to recipient cells, facilitating stem cell maintenance, differentiation, self-renewal, and repair. It has become apparent that stem cell-derived exosomes mediate interactions among stromal elements, promote genetic instability in recipient cells, and induce malignant transformation. This review will therefore discuss the potential of stem cell-derived exosomes in the context of stromal remodeling and their ability to generate cancer-initiating cells in a tumor niche by inducing morphologic and functional differentiation of fibroblasts into tumor-initiating fibroblasts. In addition, the immunosuppressive potential of stem cell-derived exosomes in cancer immunotherapy and their prospective applications in cell-free therapies in future translational medicine is discussed.Authors acknowledge the CAPES (Coordination for the Improvement of\ud Higher Education Personnel), FAPESP (Sao Paulo Research Foundation), and FAEPA (Foundation for Teaching Support, Research and Assistance from Hospital of Clinics of Medical School at Ribeirão Preto, University of São Paulo) Brazil