Mice healed three times faster than normal after their broken bones were flooded by proteins naturally used to regrow new tissues. The discovery raises the possibility of a stem cell–free route to regeneration.
The Wnt family of proteins used in the mice are involved in healing many other types of tissue; the researchers hope they will find many other uses for them.
“Gut, skin, brain, muscle, cardiac muscle, corneas, retinas — people have studied the role of Wnt signals in all those tissues,” said Stanford University reconstructive surgeon and study co-author Jill Helms. “Maybe there could be a therapeutic approach to all this.”
The experiment, published April 28 in Science Translational Medicine, is rooted in two decades of research on Wnt genes and proteins, which play a variety of regenerative roles. They help embryonic stem cells make copies of themselves, keeping a body’s supply fresh, and guide the maturation of stem cells into specific cell types.
Wnt proteins are found throughout the animal kingdom, from sponges and flatworms to mice and humans, and their function seems to be consistent. When tissues are injured, Wnt genes in surrounding cells become more active, pumping out extra Wnt proteins. Arriving repair cells divide faster and grow more rapidly.

Study co-author Roel Nusse, a cell biologist at Stanford, has pioneered much of the Wnt research. He was responsible for cloning the Wnt family genes, allowing proteins to be produced in tissue cultures in a lab. His success encouraged the study’s other authors to see if the proteins could be used therapeutically.
“This pathway may be the key to regenerating, or at least rapidly repairing, tissues,” said Helms. “We’re augmenting nature’s own response to injury.”
The researchers started their tests by genetically engineering a strain of mice that produced exceptionally high amounts of Wnt proteins. Three days after their bones were broken, they grew three and half times more new bone tissue than regular mice.
That test’s purpose wasn’t to investigate a role for genetic engineering, but rather to see if extra Wnt had an effect. The researchers next injected lab-grown Wnt proteins into mice with broken bones. These again healed three times faster.
There were no obvious side effects from the treatment, though the tests were preliminary. Somewhat disturbingly, Wnt genes were originally identified while malfunctioning in cancerous cells. The likelihood of causing cancer is also a major obstacle to developing safe stem cell therapies. But Helms is confident that it won’t be a problem with potential Wnt therapies.
“In cancer, mutations cause the pathway to be always on. Delivering the protein only causes the pathway to be turned on for a moment,” she said. “Mutations in the insulin pathway also cause cancer, but insulin treatments do not.”
According to Thomas Einhorn, a Boston University biochemist and orthopedic surgeon who wasn’t involved in the study, Wnt is an alluring therapeutic target. Malfunctions in Wnt regulation have been linked to human bone disorders, underscoring their importance. But he cautioned that “animal studies are animal studies, and human conditions are something else.”
In mice, challenges still remain. A broken bone is relatively easy to target with an injection, but many conditions are less localized, involving entire organs or large amounts of tissue.
The researchers are now conducing mouse tests of Wnt proteins for skin wounds, stroke and heart-attack recovery, and cartilage injuries.
“Nature uses this recipe over and over again,” said Helms.
Image: Healing in the skeletal tissues of mice given a placebo (top) and Wnt proteins (bottom).
Science Translational Medicine.
See Also:

• Salamander Discovery Could Lead to Human Limb Regeneration
• Engineered Rabbit Penises Raise Human Hopes
• Going From One Cell Type to Another Without Using Stem Cells
• Severed Gecko Tails Have a Mind of Their Own

Citation: “Wnt Proteins Promote Bone Regeneration.” By S. Minear, P. Leucht, J. Jiang, B. Liu, Y. A. Zeng, C. Fuerer, R. Nusse, J. A. Helms. Science Translational Medicine, Vol. 2 No. 29, April 28, 2010.
Brandon Keim’s Twitter stream and reportorial outtakes; Wired Science on Twitter. Brandon is currently working on a book about ecological tipping points.