Stories about: zebrafish

New research on blood stem cells takes root

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Word cloud of words associated with hematopoietic stem cells and blood development.
The demand for hematopoietic stem cell transplants is rising. But how can we get more cells? (Text from Bryder D, Rossi DJ and Weissman IL. Am J Pathol 2006; 169(2): 338–346.)
You need a lot of hematopoietic stem cells to carry out a hematopoietic stem cell transplant, or HSCT. But getting enough blood stem cells can be quite a challenge.

There are many HSCs in the bone marrow, but getting them out in sufficient numbers is laborious—and for the donor, can be a painful process. Small numbers of HSCs circulate within the blood stream, but not nearly enough. And while umbilical cord blood from newborn babies may present a relatively rare but promising source for HSCs, a single cord generally contains fewer cells than are necessary.

And here’s the rub: The demand for HSCs is only going to increase. Once a last resort treatment for aggressive blood cancers, HSCTs are being used for a growing list of conditions, including some solid tumor cancers, non-malignant blood disorders and even a number of metabolic disorders.

So how do we get more blood stem cells? Several laboratories at Boston Children’s Hospital and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center are approaching that question from different directions. But all are converging on the same end result: making more HSCs available for patients needing HSCTs. …

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Zebrafish make a big splash

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If you look at the range of research models available to scientists today (from fungi to flies to mice and larger), one little guy stands out – a tropical freshwater fish from the rivers of Bangladesh called the zebrafish. While it may be small, this fish is having a big impact on medical science, especially in genetics, stem cell biology, and drug screening, as covered in today’s Wall Street Journal.

As we’ve mentioned previously on Vector, the zebrafish is swimming its way into many research programs, both here at Children’s Hospital Boston and across the country. As a model, they are quite attractive to researchers, in part due to their small size, their fecundity, and their surprising similarities to us (from a genetic standpoint, that is).

Richard White, who works with Leonard Zon in the Stem Cell Program at Children’s Hospital Boston, offers up an explanation for the fish’s popularity:

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From fish to people – first drug ID’d in zebrafish crosses a milestone

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A recent clinical trial brings the drug FT1050 one step closer to becoming the first drug identified with the help of zebrafish (above) to make it to patients. (Soulkeeper/Wikimedia Commons)

In 2007, working with zebrafish, Leonard Zon and his team in Children’s Stem Cell Program made an unexpected discovery: That a drug originally developed to treat stomach ulcers could boost the production of blood stem cells, by about four-fold.

That drug – FT1050, a chemical variant of a fatty, hormone-like molecule called prostaglandin E2 (PGE2) – recently crossed a major milestone: the successful conclusion of a Phase I clinical trial. Led by Zon’s colleague Corey Cutler, a clinical researcher at Dana-Farber Cancer Institute, the trial aimed to determine the drug’s safety as a way of helping patients who receive umbilical cord blood stem cell transplants recover their immune function more quickly.

The trial brings the FT1050 one step closer to becoming the first drug identified with the help of zebrafish to make it to patients. …

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The iSpawn: The birds, the bees, and the zebrafish

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One of the characteristics that make zebrafish a fantastic model for research is that they spawn…a lot. A healthy female zebrafish can lay upwards of 1,000 eggs each week. By comparison, the mouse, another species widely used in research, may have a single 12-pup litter each month.

Sometimes, though, that isn’t enough. A researcher screening a library of chemicals for potential drugs, for instance, might need tens of thousands of zebrafish embryos, all at the same developmental stage, to have statistically meaningful results.

That researcher could really use the iSpawn.

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The fish are biting

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The zebrafish (above, in a microtiter well) packs a lot of research punch in a small package.
They’re small, they’re transparent, and they breed at an amazing rate. They may hold the key to understanding the genetics of many human diseases. And they may help scientists discover new drugs – quicker and cheaper. Oh, and they’re fish.

The zebrafish (Danio rerio to the taxonomists) is a striped tropical fish, no longer than your pinky finger, that looks like it would be more at home in someone’s aquarium than in a laboratory. But for several reasons, zebrafish are powerful organisms for stem cell, developmental, and genetic research:

  • Despite our distance from zebrafish on the evolutionary tree, they’re surprisingly similar to us from a genetic standpoint.
  • Because of their small size, they can be housed at high densities.
  • Compared to other model organisms like mice, they’re relatively inexpensive to care for.
  • An adult female zebrafish can lay 300 eggs each week. By comparison, a mouse might have a single 12-pup litter each month.
  • Their skin is permeable, so they can absorb drugs directly from the water of their tank.
  • Zebrafish embryos are transparent, offering a window into their bodies; some lines, like Casper, remain transparent through adulthood. …
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