Making Stem Cells

Researchers at Duke Medical Center have demonstrated that they can grow human stem cells in the laboratory by blocking an enzyme that normally triggers stem cells to mature and differentiate into specialized cells. The discovery may enable scientists to grow stem cells rapidly and transplant them into patients with blood disorders, immune defects, and select genetic diseases.

Stem cells are the most flexible cells in the body, continually dividing into new stem cells or into specialized cells that carry out specific roles. But little is known about how stem cells choose their fate. The Duke team focused on blood or "hematopoietic" stem cells. In their study, the investigators discovered that an enzyme called aldehyde dehydrogenase (ALDH) stimulates hematopoietic stem cells to differentiate into blood or immune cells. Inhibiting this enzyme in stem-cell cultures increased the number of stem cells more than threefold. They also demonstrated that the new stem cells were capable of fully rebuilding the blood-forming and immune systems of immune-deficient mice.

Results of the study were published in the Proceedings of the National Academy of Sciences.

Currently, patients who require stem-cell transplants are given either bone marrow from adult donors, umbilical-cord blood, or stem cells from blood. But stem cells are scarce, representing less than .01 percent of the bone-marrow cell population. Likewise, cord blood units frequently lack sufficient numbers of stem cells to rebuild a patient's decimated immune system.

Efforts to grow human hematopoietic stem cells in the laboratory have proved extraordinarily difficult, says John Chute, associate professor of medicine in the Duke Adult Bone Marrow and Stem Cell Transplant Program, because growth factors in culture make stem cells rapidly differentiate.

"Our ability to treat human diseases is limited by our knowledge of how human stem cells determine their fate—that is, whether they maintain their ability to self-renew or whether they go on to become specialized cells," Chute says. "Unraveling the pathways that regulate self-renewal or differentiation in human stem cells can facilitate our ability to expand the growth of human stem cells for therapeutic uses."