Scientists led by Leonard Zon, a Howard Hughes Medical Institute researcher at Children's Hospital in Boston, have discovered that zebrafish produce natural chemicals that enhance production of blood-forming stem cells. Their study’s surprising results may translate rapidly into new treatments to increase the success of bone marrow or cord blood transplants in humans.
In their experiments, the researchers were searching for compounds that would increase the production of blood-forming, or hematopoietic, stem cells (HSCs). Such compounds could be clinically important in enhancing the success of bone marrow and cord blood transplantation. The researchers screened a library of 2,275 chemicals, about a third of which are already FDA-approved, said Zon. They began by placing fish embryos in the tiny wells of a culture dish. Once the embryos were in place, the researchers added one of the chemicals, stained the embryos for stem cells, and observed whether the chemical enhanced or decreased stem cell production. The scientists identified 35 compounds that increased HSC production and 47 that decreased it.
Further exploration revealed that the prostaglandin E2 (PGE2) in the zebrafish played a central role in regulating HSC formation. When they administered a long-acting version of PGE2 to fish embryos, they saw a considerable enhancement of stem cell production. Prostaglandins are fatty hormone-like chemicals known to regulate a wide array of body processes.
In additional studies with both adult zebrafish and mice, they found that the long-acting PGE2 greatly enhanced HSC production. Conversely, inhibiting PGE2 diminished HSC production. In particular, when they transplanted both PGE2-treated and untreated stem cells into mice, the treated cells far outperformed the untreated cells in their ability to proliferate.
While the HSC-enhancing drugs they identified could find use in aiding marrow transplantation, they will likely be especially important in cord blood transplantation, said Zon.
Children's Hospital in Boston now hopes to conduct a clinical trial of the drug in 2008, a long-active derivative of prostaglandin E2 known as dmPGE2. This compound was originally tested more than 20 years ago for patients with gastritis, but was never marketed as a drug.
14 WFIE (06/20/07)
Sawf News (06/20/07)
Howard Hughes Medical Institute (06/21/07)
United Press International (06/22/07)