Lighting the Way

The mice in Steven Ebert’s lab are glowing.

“They glow just like a firefly would glow,” said Ebert, a biomedical researcher at the University of Central Florida in Orlando. In each mouse’s heart are thousands of embryonic stem cells, shining brighter and brighter as they become functioning heart muscle.

Tracking stem cells as they develop is a key step towards understanding how these cells might be used to treat anything from cardiac disease to blindness. Because stem cells can become all different kinds of tissue, they are prime candidates for regenerating damaged organs. Ebert’s most recent work, published in September in the journal Stem Cells and Development, could help researchers better understand how this happens.

One of the current challenges of stem cell therapies, said Ian Gallicano, a biochemist at Georgetown University in Washington, D.C. who was not involved in the research, is that researchers don’t know exactly how they work. Once stem cells are injected into the body, they can become indistinguishable from the rest of the approximately sixty trillion cells that make up a human.

By inserting an extra gene into the stem cells—the same gene that produces light in fireflies—Ebert has helped to solve this problem. His group injects the engineered stem cells into the mouse’s chest, near the heart. When the cells glow, scientists can actually see how they’re behaving, where they’re going, and what they’re doing.

To the naked eye, Ebert’s subjects just look like your average lab mice—you can’t see the glow through the layers of blood, bones and skin. To see the light Ebert and his team place the mice into a small black box, about the size of a dorm room refrigerator, where an extremely sensitive camera photographs the glow through their skin.

From these pictures, Ebert and his team can see how many cells are working, where they’re active, and whether they’re becoming the right kind of tissue. The gene that stimulates light in the injected stem cells only starts working when the cells become heart muscle, so only stem cells that have become heart muscle will show up on the pictures.

Not only can the scientists see where the cells are and what they’re doing, but Ebert’s research allows them to do so without sacrificing the animals. “The beauty of bioluminescence,” said Stanford University cardiologist John Cooke, who didn’t work on the project, “is that you can do this non-invasively and the animals survive the process.”

This study used healthy mice, but Ebert’s next step will be to see how the cells behave in mice with heart disease. He hopes to see the glowing cells congregate around the damaged hearts, indicating regeneration.

Ebert doesn’t plan on making any glowing people in the near future; these cells aren’t meant for human use. In the mice, he explained, the light only has to travel through a few millimeters of tissue to reach the outside world. To see a glow from human hearts would be much more difficult, because the light would have to pass through many more layers of tissue. Instead he plans to use the information he and his colleagues gain from these models to improve their treatment strategies for humans.

“We still have so much to learn about these cells and all that they really may be capable of,” said Rosalinda Castaneda, a radiologist at Stanford who was not part of Ebert’s team. Using imaging techniques like this one, scientists hope to develop stem cell treatments for the over 60 million Americans with heart disease.

“There’s a whole big mess that goes on with the normal progression of heart disease,” Ebert said, “but if we had the capability to introduce stem cells that could replace or regenerate heart muscle, that would really advance the field.”