Described herein are compositions and techniques related to generation and therapeutic application of stem cell-derived exosomes. The Inventors have discovered cardiosphere-derived cells (CDCs) and their secreted exosomes mediate such inflammatory processes, by, for example, shifting macrophages away from a proinflammatory M1 phenotype toward M2 healing phenotype. This suggests compositions and techniques for use in both long-term reversal of heart and vascular disease pathology, and protection against such disease progression via modulation of inflammation and immune responses.