Every day, millions of stem cells zip around our bodies, creating new tissue and helping our organs function correctly. But when one of these cells travels somewhere it's not supposed to go, the result can lead to a tumor. So studying just how these vital cells move is a critical step to understanding cancer. Researchers at the University of Oxford have just provided a window into this process by building a machine that beams flatworms with x-rays that kill just enough stem cells to allow the others to move freely around while being tracked.
Flatworms, or planarians, make good test subjects because of their regenerative abilities; cut off a piece of one, and it will grow back. In fact, earlier this year, it was discovered that a flatworm that had been cut in half and sent to the International Space Station returned to Earth having two heads because it had grown one on the missing half when it was regenerated.
The stem cells inside planarians are key to the worm's superhero-like abilities. Known as neoblasts, they can grow into any organ inside the worm's body and can lead to an entirely new worm in just a few weeks. These cells also divide continuously, so there tend to be a lot of them. This caused a paradoxical problem for the researchers looking to study them.
"Perhaps a little counterintuitively, the sheer abundance of stem cells in planarians makes it difficult to study migration," said Aziz Aboobaker, head of Oxford's regeneration lab and no stranger to flatworms. "In order to trace the movement of cells you need to create a field for them to move into so you can be sure of the direction and speed at which they're moving, but if the cells you are interested in are already everywhere that is difficult to do."
So, Aboobaker and his team looked at the plentiful research on flatworms and found one study in which a flatworm could survive getting beamed with x-rays, as long as part of the animal was protected by a lead shield. "Presumably the stem cells under the lead shield migrate to the rest of the animal and everything is fine," said Prasad Abnave, first author of the study published in the journal, Development.
Working with a doctor from Oxford's oncology department, the team created a machine that could bombard the worms with stem-cell-killing x-rays except for a small strip where the stem cells survived thanks to shielding. The researchers could then watch those stem cells flood into the worms' bodies, studying their pathways and their movements.
"It sounds simple, but it took a long time to design an apparatus and techniques with which we could study many worms at once," said Aboobaker. "That was key in being able to study how migration was controlled and for performing high-quality experiments that could really generate reproducible results."
While the technique now needs to be applied in earnest to studying the movement of stem cells and their relationship to cancer development, the team did uncover two things.
First, they found that stem cells streamed to the site of an injury in the worms, but when the animals were left unharmed, the stem cells didn't move at all. Second, by blocking the function of genes involved in stem cell migration, the researchers were also able to keep the stem cells in the worms stationary.
"This was a very satisfying result as it confirmed our suspicion that our simple worms will be very useful for understanding stem cell migration, now we have proven the system we can look intensely for new mechanisms that control or interact with cell migration and have a real expectation that we find will also be true for our migrating cells," said Abnave. "One advantage of our worms is that they are easy to work with and we can make rapid progress."
Source: University of Oxford