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Fishing for a Speedy Recovery After Chemotherapy or Marrow Transplant

ing more than 2,500 chemicals in zebrafish. Knowing that two genes, runx1 and cmyb, are required for blood stem cells to develop in vertebrate embryos, they looked for compounds that altered the expression (activation) of these genes. North spent six months placing 15,000+ tiny embryos in wells, each containing a different chemical five embryos to a well, 48 wells to a plate then checking each embryo 24 hours later to monitor its development and count its blood stem cells.

The screen identified 82 chemicals that markedly increased or decreased gene activity. Of these, 10 turned out to affect the prostaglandin pathway: five increased the formation of blood stem cells, and five decreased it. We werent specifically looking for prostaglandins, says Zon, a Howard Hughes Medical Institute investigator who is also a member of the Harvard Stem Cell Institute. This was a surprise finding.

A variety of experiments confirmed that prostaglandins, particularly dmPGE2, promote blood stem cell formation, while chemicals that block prostaglandin synthesis (such as aspirin or ibuprofen), suppress blood stem cell formation. Finally, in zebrafish whose marrow was depleted by irradiation, those given dmPGE2 recovered blood cell populations more quickly.

Prostaglandins are known to be released by the body when inflammation is present such as after an injury and may be among the compounds that aid recovery. So it makes some sense that prostaglandins would have the ability to enhance regrowth of cells, Zon says.

The zebrafish is ideal for investigating blood formation, says North. It reproduces quickly and in large number and has a blood-forming system that shares many similarities with that of mammals. Zebrafish embryos develop outside the mothers body and can take up chemicals through their skin, making it easy to test the developmental effects of large numbers of compounds very rapidly, while their transparent skin makes it p
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