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See-Through Zebrafish

Feb. 12, 2008

Transparent zebrafish, described in the Feb. 7 issue of the journal Cell Stem Cell, are allowing researchers at Children's Hospital Boston to directly view internal organs and observe processes such as tumor growth in real-time in living organisms.

While scientists have studied disease in the embryos of zebrafish, which are naturally transparent, their bodies turn opaque as adults. The newly created fish stays transparent throughout its lifetime. "Everything after four weeks has been invisible to us," said study team member Richard White, a clinical fellow in the Stem Cell Program at Children's Hospital Boston.

White created the transparent fish, which he nicknamed Casper, by mating two existing zebrafish breeds, one that lacked a reflective skin pigment and the other without black pigment. The offspring had only yellow skin pigment, essentially appearing clear.

In one experiment, White and his colleagues inserted a fluorescent melanoma tumor into the abdominal cavity of the transparent fish. By observing the fish under a microscope, they found that the cancer cells started spreading within five days. White could actually see individual cells spreading.

"The process by which a tumor goes from being localized to widespread and ultimately fatal is the most vexing problem that oncologists face," White said. "We don't know why cancer cells decide to move away from their primary site to other parts in the body."

The spreading melanoma cells appeared to flock toward the skin after leaving the abdominal cavity. "This told us that when tumor cells spread to other parts in the body, they don't do it randomly," White said. "They know where to go."

White ran a similar experiment in which he transplanted fluorescent blood-forming stem cells from another zebrafish into a transparent one. By four weeks, the stem cells had visibly moved into the see-through fish's bone marrow and started growing.

Marrow, the soft fatty tissue inside bones, supports stem cells that each ultimately become a type of blood cell, which gets released into the bloodstream. Any disease that disrupts the production of mature blood cells or their precursors can cause a bone marrow disorder, such as leukemia.

While transplants of blood-forming stem cells help cancer patients rebuild healthy blood, for unknown reasons some transplants don't "take." If researchers could understand the step-by-step process in which the stem cells embed and build blood in the fish, they could figure out ways to help patients rebuild their blood faster.

Source: ScienceDaily


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