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Something Fishy About Stem Cell Treatment?

HealthNewsDigest.com, June 21, 2007

New treatments to amplify the success of cord blood and bone marrow transplants in humans could be developed thanks to a new discovery related to zebrafish. Blood-forming stem cell production is enhanced due to a natural chemical that is produced by the fish.

The finding was published in the June 21, 2007 issue of the journal Nature. At the Children's Hospital in Boston, Leonard Zon, a Howard Hughes Medical Institute researcher, led the team. The lead author of the study was a postdoctoral fellow in Zon's laboratory named Trisha North.

“Using drugs that enhance PGE2 to amplify the number of stem cells in a cord [blood] sample could enable use of only one cord in such patients," said Zon.

Hematopoietic stem cells (HSC's) are blood forming cells. The researchers wanted to find a compound that would increase the production of these cells during their experimentation. The success of cord blood treatments and bone marrow transplants could be enhanced by these special compounds according to Zon. For example, a clinically significant breakthrough could potentially be used to improve the treatment of patients who have lost the majority of their blood cells due to cancer therapy. Those patients could utilize bone marrow or cord blood to restore their immune systems. A compound that could boost the production of blood forming stem cells would be highly beneficial in patient treatment.

“In earlier work, we developed staining methods that marked HSCs in the developing zebrafish embryo,” said Zon. “Since we can produce and test thousands of zebrafish embryos at a time, we have a very quick and efficient model for large-scale testing. So, Trista and I came up with the idea of conducting a mass screening of chemicals from a library to see whether we could find any that increased the quantity of stem cells.”

Zon said that about a third of the 2,275 chemicals his team screened were already approved for use by the FDA. They began by placing fish embryos in the tiny wells of a culture dish. The researchers observed whether stem cell production was decreased or enhanced after staining the embryos for stem cells and then adding one of the chemicals. 47 compounds were found to decrease the production of HSC's, however, 35 compounds were found to increase production. The door leading to the understanding of the regulatory mechanism for stem cells was also opened a bit more during the experiments.

“When we looked at the list of chemicals that affected stem cells, what was staring us in the face was that many acted on the prostaglandin regulatory pathway,” said Zon. “This prompted us to explore this pathway in more depth.”

Known to regulate a wide array of body processes, prostaglandins re fatty hormone-like chemicals.

The regulation of HSC formation was observed to be significantly effected by the prostaglandin E2 (PGE2) in the zebrafish during further exploration. The researchers observed a considerable enhancement in stem cell production when they administered a long-acting version of PGE2 to the fish embryos.

Additional studies revealed that HSC production was enhanced by long acting PGE2 in both mice and adult zebrafish. Production was decreased when PGE2 was inhibited. The ability of stem cells to proliferate was effected when untreated mice were compared to PGE2-treated mice. The stem cells that were injected with the PGE2 significantly outperformed the untreated cells in proliferation.

Researchers found that stem cell production was decreased when—cox 1 and cox 2—two regulators of PGE2 was also decreased. Zon said that since pain medications such as ibuprofen and aspirin are cox inhibitors, the finding would be important for human bone marrow recipients.

Zon stated that cord blood transplantation would be most impacted by the identification of HSC-enhancing drugs, even more so than in marrow transplantation. Immune compromised patients are treated with umbilical cord blood stem cells in order to restore the immune system in this particular treatment.

“Cord blood has a limited number of stem cells in it, enough so that the blood from a single cord is sufficient for a small child. However, when it is transplanted into an adult, there is a 40 percent chance that the patient won't engraft, because there aren't enough stem cells in the sample,” said Zon. “When adult patients are given two cords from unrelated donors, this chance of failure is reduced, but there may be immunological problems from interaction between the two sources."

“Using drugs that enhance PGE2 to amplify the number of stem cells in a cord sample could enable use of only one cord in such patients,” said Zon. “And it may even help patients who don't engraft.” Zon said he and his colleagues plan to begin clinical trials of such HSC-enhancement using the long-acting version of PGE2.


 

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