Seeing the shimmer of biology in action  pg. 5

Islet transplantation is an emerging experimental therapy for type 1 diabetes and has shown promise in multiple small clinical trials. One difficulty in moving the field forward, Powers explains, is that investigators have no way to follow the islets after transplantation.

Human pancreatic islets glow after infection with a virus carrying the firefly's light-producing luciferase gene.  Number of islets in each well:  (top row, from left) 0, 1,000, 50; (bottom row) 100, 500, 1,000.  The 1,000 islets in the middle well of the top row were not infected, do not produce the luciferase enzyme, and therefore do not emit light.
Image courtesy of Alvin C. Powers, M.D.
“We really need a way to assess where the islets go after transplantation, how many survive, (and) what kinds of therapies promote islet survival,” Powers says.

In collaboration with Jansen, Powers and colleagues have “tagged” islets with luciferase. They have used primarily a strategy of infection: first the investigators harvest islets, both from mice and humans, then they infect the islets with a virus carrying the luciferase gene. A certain percentage of the islet cells incorporate the luciferase, and after transplantation into a mouse the surviving cells can be followed with bioluminescence imaging.

The team is also beginning to use islets from genetically modified mice that have luciferase in all of the beta cells of the islet. These light-emitting islets offer the advantage that all cells permanently express the luciferase.

In both models, the investigators are attempting to optimize transplantation parameters, Powers says. What is the best site for survival? Which growth factors best promote survival? Is it best to treat the islets with growth factors before transplantation, to treat the animals after transplantation, or both?

“Bioluminescence is really the only way to non-invasively assess these islets over time,” Jansen says. He notes that it would be possible to sacrifice animals to get single time-point snapshots, but that methodology would require a very large number of animals and retain the problem of biological variation between individuals. Non-invasive imaging of any sort, in the same animal over time, gives the best statistical results by avoiding interindividual variability, he says.

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