The online journal Scientific Reports recently detailed a study from Johns Hopkins Medicine showing support for previous research that a cellular protein signal facilitates the formation of both bone and fat in particular stem cells. The study also shows that this protein signal can be influenced to build bone.
The researchers believe that manipulating the protein, also known as WISP-1, in favor of building bone could mean healing fractures more quickly, reducing surgical recovery times and potentially preventing bone loss that occurs as a consequence of aging, injury and illness.
"As we age, the body slows down the production of bone cells, and as a result, we lose bone mass," said Dr. Bill Johnson, a Dallas, Texas, stem cell physician.
Stem cells are regenerative cells with the ability to develop into a wide range of tissues. Stem cells also can regenerate without limit to replace or repair tissue that has been injured or damaged by disease.
"When tissues or organs become impacted by injury or illness, they put off a signal to stem cells hibernating in the area to wake up and get to work," Johnson said.
Cell signaling is a critical part of how cells function; it governs cell activities, including development, immunity, day-to-day function and maintaining the cell environment and tissue repair. The Johns Hopkins researchers hope that by changing how WISP-1 behaves they can coax a specific type of stem cells called perivascular stem cells into becoming bone instead of fat.
During the study, the Maryland researchers used genetically engineered stem cells to block the body from producing the WISP-1 protein. They then analyzed the gene activity of cells without WISP-1 and found that four genes that trigger fat cell formation were present at levels that were 50 to 200 percent higher than control cells containing normal levels of protein.
The researchers' next step was to create human fat tissue stem cells with the ability to produce more WISP-1 protein than normal cells. They found that the genes that control the formation of bone were twice as active in these new cells. They also found that the activity of the fat-creating genes was reduced by 42 percent.
The next phase of the project involved testing whether the WISP-1 protein could be used to improve bone healing times. To do so, they used rats that underwent spinal fusion, a procedure that is performed on people to reduce pain or restore stability by fusing vertebrae using a metal rod so that they grow into a stronger, single bone.
According to the U.S. Agency for Healthcare Research and Quality, there are 391,000 spinal fusions are performed in the U.S. each year.
Recovery from a spinal fusion procedure takes between four and six weeks and requires a significant amount of rest while new bones cells are formed. Speeding up the process of bone-cell generation could mean that long periods of rest - and the risk of complications - can be reduced.
In addition to mimicking the human surgical procedure in the rats, the researchers also injected human stem cells with the WISP-1 protein between the newly fused spinal bones.
Four weeks after the procedure, the researchers examined the spinal tissue of the test rats and noticed high levels of the WISP-1 protein, as well as new bone forming. Rats that did not receive WISP-1 protein injections did not show successful bone fusion during the four-week post-surgery period.
These findings show promise and potential for treating fractures caused by injury and bone disease. According to the Office of the Surgeon General, 1.5 million Americans suffer a bone disease-related fracture annually.
The Johns Hopkins team also hopes their research could be used to increase the production of fat cells to help treat the healing of soft-tissue wounds as well.
Johns Hopkins Medicine. "Stem cell signal drives new bone building: If harnessed in people, it could speed recovery for bone breaks, spinal fusions, osteoporosis." ScienceDaily. ScienceDaily, 7 January 2019.