Resveratrol for ex vivo purging of hematopoietic autografts

Novel purging strategies that would selectively eliminate contaminating tumor cells without affecting the hematopoietic activity of progenitor cells are needed for ex vivo purging of autografts. In this study we demonstrate that resveratrol, a chemopreventive agent naturally present in grapes, exhibits antiproliferative activity against mouse and human leukemic cell lines. Long term exposure to resveratrol also inhibited the clonal growth of normal hematopoietic progenitor cells but at a higher IC50 than the leukemia cell lines tested. The inhibitory effect of resveratrol on hematopoietic progenitors is reversible, whereas the effect on leukemia cells is largely irreversible. Resveratrol induced apoptosis in leukemia cells, but it neither induces or enhances the spontaneously occurring DNA fragmentation in normal progenitor cells. More importantly, in vivo experiments demonstrated that treatment of bone marrow cells with resveratrol does not impair their ability to engraft in lethally irradiated mice. Overall, these data indicate that resveratrol may be used for pharmacological purging of autografts without significant decrease in the hematopoietic activity of progenitor cells.