Project Summary: Exosomes are small, naturally occurring nanovesicles that facilitate cellular communication. Exosomes are now being viewed as potential therapeutic agents in multiple organ systems. Our preliminary data show that human breast milk derived exosomes (HBMDE) protect intestinal epithelial cells from oxidative stress by decreasing inflammation and up regulating protective proteins. Although these results are promising, not all premature infants have access to the therapeutic benefit of their own mother’s breast milk. Currently the recommendation for infection and communicable disease prevention prevent sharing of fresh breast milk from another infant’s mother. Breast milk donor banks have largely addressed this problem by allowing infants access to pasteurized pathogen free breast milk. Recent evidence suggest that exosomes are present in pasteurized donor milk, but it is not known if they have the same therapeutic benefit and immune profile of non-pasteurized fresh human milk exosomes. To date, exosomes have not been used as a systemic multi-organ therapy to reduce cellular injury. The potential use of donor milk exosomes would greatly accelerate this relatively new treatment strategy. This proposal will provide a comprehensive analysis on the immunogenic and therapeutic properties of pasteurized HBMDE.