New York, NY (June 7, 2002) In a new study just published in the journal Circulation Research, scientists at Weill Cornell Medical College demonstrate that therapy with bone-marrow-derived precursor cells can restore aging cardiac blood vessel-forming capacity, thus possibly preventing some of the morbidity and mortality associated with ischemic heart disease in older individuals. The study points to a promising and novel approach to preventing and treating heart disease in the aging.

The lead author, Dr. Jay Edelberg, Assistant Professor of Medicine in the Division of Cardiology at Weill Cornell and Assistant Attending Physician at NewYork-Presbyterian Hospital’s Weill Cornell Medical Center, says the study, in an animal model, builds on previous research in his lab that examined changes in the endothelial cells that line the blood vessels of older hearts. That study found that molecular alterations in those aged cells lead to a dysregulation of a molecular pathway by which platelet-derived growth factor (PDGF) normally contributes to angiogenesis, or new blood vessel formation. In the new study, he and his colleagues show the possibility of restoring this pathway by bone marrow transplantation.

Bone marrow contains both stem cells and precursor cells of cardiac blood vessels. (Stem cells are like the trunk of a tree, and precursor cells are like the branchesstem cells divide and become precursor cells, which divide and become the functional cells of a mature organ.) Dr. Edelberg and his colleagues sought to demonstrate that bone-marrow-derived endothelial precursor cells (EPCs) can reverse the aging-associated decline in the heart’s angiogenic activity.

The authors achieved their results with mouse models both in vitro and in vivo. In vitro, when cardiac muscle cells were cultured with young (3-month-old) and old (18-month-old) EPCs, expression of beneficial PDGF was induced in the former set but not in the latter. In vivo, the investigators transplanted the bone marrow cells of young mice into older mice. The result was that the genetically-marked bone marrow cells were recruited to and engrafted in the senescent bone marrow. Furthermore, the technique stimulated the production of young bone-marrow-derived EPCs, and these helped to restore the angiogenic PDGF pathway in the older mice.

“These results may offer a foundation for the development of novel therapies for the prevention and treatment of cardiovascular disease associated with aging,” the authors write. Although it is still too early to be certain of the possibility, Dr. Edelberg says, the hope for humans is that eventually a drug might be taken to stimulate the production of bone-marrow-derived endothelial precursor cells, or that such cells might be transplanted into an older person. Either technique might lead to a rejuvenation of the aging heart.

The other authors are Lilong Tang, Koichi Hattori, David Lyden, and Shahin Rafii. Drs. Edelberg, Tang, Hattori, and Rafii are in the Department of Medicine of Weill Cornell; Dr. Edelberg is also in the Department of Cell and Developmental Biology. Dr. Lyden is in Weill Cornell’s Department of Cell and Developmental Biology and also in the Department of Pediatrics of Memorial Sloan-Kettering Cancer Center.

The study was supported by grants from the American Federation for Aging Research (Beeson Physician Faculty Scholar in Aging Research), the Ellison Medical Foundation, the Atrovastatin Research Awards Program, the Doris Duke Charitable Foundation, and the National Heart, Lung, and Blood Institute.