The skin, the blood, and the lining of the gut-adult stem cells replenish them daily. But stem cells really show off their healing powers in planarians, humble flatworms fabled for their ability to rebuild any missing body part. Just how adult stem cells build the right tissues at the right times and places has remained largely unanswered.
Now, in a study published in an upcoming issue of Development, researchers at the Stowers Institute for Medical Research describe a novel system that allowed them to track stem cells in the flatworm Schmidtea mediterranea. The team found that the worms' stem cells, known as neoblasts, march out, multiply, and start rebuilding tissues lost to amputation.
"We were able to demonstrate that fully potent stem cells can mobilize when tissues undergo structural damage," says Howard Hughes Medical Institute and Stowers Investigator Alejandro S-nchez Alvarado, Ph.D., who led the study. "And these processes are probably happening to both you and me as we speak, but are very difficult to visualize in organisms like us."
Stem cells hold the potential to provide an unlimited source of specialized cells for regenerative therapy of a wide variety of diseases but delivering human stem cell therapies to the right location in the body remains a major challenge. The ability to follow individual neoblasts opens the door to uncovering the molecular cues that help planarian stem cells navigate to the site of injury and ultimately may allow scientists to provide therapeutic stem cells with guideposts to their correct destination.
"Human counterparts exist for most of the genes that we have found to regulate the activities of planarian stem cells," says S-nchez Alvarado. "But human beings have these confounding levels of complexity. Planarians are much simpler making them ideal model systems to study regeneration."
Scientists had first hypothesized in the late 1800s that planarian stem cells, which normally gather near the worms' midlines, can travel toward wounds. The past century produced evidence both for and against the idea. S-nchez Alvarado, armed with modern tools, decided to revisit the question.
For the new study, first author Otto C. Guedelhoefer, IV, Ph.D., a former graduate student in S-nchez Alvarado's lab, exposed S. mediterranea to radiation, which killed the worms' neoblasts while leaving other types of cells unharmed. The irradiated worms would wither and die within weeks unless Guedelhoefer transplanted some stem cells from another worm. The graft's stem cells sensed the presence of a wound-the transplant site-migrated out of the graft, reproduced and rescued their host. Unlike adult stem cells in humans and other mammals, planarian stem cells remain pluripotent in fully mature animals and remain so even as they migrate.
But when Guedelhoefer irradiated only a part of the worm's body, the surviving stem cells could not sense the injury and did not mobilize to fix the damage, which showed that the stem cells normally stay in place. Only when a fair amount of irradiated tissue died did the stem cells migrate to the injured site and start to rebuild. Next, Guedelhoefer irradiated a worm's body part and cut it with a blade. The surviving stem cells arrived at the scene within days.