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Tiny exosomes extracted from donor cells may be 'magic bullet' for drug-free transplants

PITTSBURGH, Nov. 10 Bubble-like nano-scale particles that are shed by dendritic cells may hold the key to achieving transplant tolerance the long-term acceptance of transplanted organs without the need for drugs, suggests a study by University of Pittsburgh researchers published in the Nov. 15 issue of the journal Blood. The results provide some of the first information about what these structures called exosomes actually do.

Exosomes are no larger than 65-100 nanometers 1,000 times smaller than the diameter of a human hair yet each contains a potent reserve of major histocompatibility complex (MHC) molecules. MHC molecules are gene products that cells use to determine self from nonself. Millions of exosomes scurry about within the bloodstream, and while their function has been somewhat of a mystery, researchers are beginning to surmise that they play an important role in immune regulation and response.

Adrian Morelli, M.D., Ph.D., of the University of Pittsburgh's Thomas E. Starzl Transplantation Institute, became intrigued by the tiny exosomes while researching ways to harness dendritic cells, specialized white blood cells that present antigens to other immune system cells, as a means to donor-specific immune tolerance. Considered the "Holy Grail" of transplantation, tolerance means a recipient's immune system fully accepts a donor graft without immunosuppressive drugs and without compromising its ability to respond appropriately to infections. Because certain dendritic cells have tolerance-enhancing qualities, several approaches under study involve giving recipients donor dendritic cells that have been modified in some way. The idea is that the modified donor cells would convince recipient cells that a transplanted organ from the same donor is not foreign.

"What may be a more effective approach is to make use of these tiny, MHC-rich vesicles that we can siphon from donor dendritic cells and that we have found are captured by recipie
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10-Nov-2004


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