AbstractCertain proteins, including fibroblast growth factor‐2 (FGF‐2) and matrix metalloproteinase‐9 (MMP‐9), have proved very effective in increasing the efficacy of mesoangioblast stem cell therapy in repairing damaged tissue. We provide the first evidence that mouse mesoangioblast stem cells release FGF‐2 and MMP‐9 in their active form through the production of membrane vesicles. These vesicles are produced and turned over continuously, but are stable for some time in the extracellular milieu. Mesoangioblasts shed membrane vesicles even under oxygen tensions that are lower than those typically used for cell culture and more like those of mouse tissues. These findings suggest that mesoangioblasts may themselves secrete paracrine signals and factors that make damaged tissues more amenable to cell therapy through the release of membrane vesicles. J. Cell. Physiol. 224:144–151, 2010 © 2010 Wiley‐Liss, Inc.