In a study published today in Science Translational Medicine, a team of researchers led by Michael Longaker, MD, and instructor Charles K. F. Chan, PhD, reveal the reason for the impairment and demonstrate a potential solution.
The project began when Longaker, who co-directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, and his colleagues identified a population of stem cells in mice, called skeletal stem cells, or SSCs, that can give rise to all components of the skeletal system. They further observed that, when these cells were depleted, fracture healing in the animals was severely impaired. They wondered if something similar could be happening in diabetes.
From our release:
The researchers used a mouse model of Type 2 diabetes, in which the disease arises when the animals are about 4 weeks old. Prior to the development of the disease, the prediabetic mice were able to heal leg bone fractures as effectively as wild-type mice, the researchers found. In contrast, after the disease had manifested itself, the repaired bone was significantly weaker and less dense than the bone in the control animals. When they compared the numbers of SSCs in the healing bone seven days after fracture, they found that the diabetic mice had significantly lower numbers of these cells than did the control animals.
Longaker, Chan and their colleagues tracked the problem down to the signal that the cells were, or weren’t, receiving from their surrounding environment. An inflammatory molecule that is known to be elevated in mice and humans with diabetes blocks the activity of a signaling pathway involved in activating the bone stem cells. They collaborated with bioengineer Fan Yang, PhD, and research associate Xinming Tong, PhD, to design a biofriendly hydrogel impregnated with the signaling molecule missing in the animals and applied it directly to the fracture site. Diabetic mice treated in this way were able to heal fractures just like normal mice.
Finally, the researchers collaborated with orthopaedic surgeon Stuart Goodman, MD, PhD, to examine bone from diabetic patients who had undergone joint replacement. They found that, like in the mice, the bone from these patients expressed lower levels of the signaling molecule that activates the bone stem cells.
As Longaker explained:
We’ve uncovered the reason why some patients with diabetes don’t heal well from fractures, and we’ve come up with a solution that can be locally applied during surgery to repair the break. Diabetes is rampant worldwide, and any improvement in the ability of affected people to heal from fractures could have an enormously positive effect on their quality of life.
Previously: To boldly go into a scar-free future: Stanford researchers tackle wound healing, Your aging pancreas and you: Researchers chart diabetes-related changes over time and Calcium the conductor: New role found for mineral in bone development
Photo by James Lee