‘Coaxing’ stem cells to form new bone tissue
Stem cells are undifferentiated cells that have the potential to specialize and undertake any function.
Much recent research has focused on how best to use stem cells for therapeutic purposes. Researchers are particularly interested in how to manipulate them to create new tissue that can successfully replace damaged sets of cells or those that are no longer functional.
In a new study from the Johns Hopkins University School of Medicine in Baltimore, MD, Dr. Aaron James and his team have looked into the mechanisms that allow certain types of stem cell, which are known as “perivascular stem cells,” to form new bone tissue.
These stem cells tend to turn into either fat tissue or bone tissue. To date, it has been unclear what, exactly, determines their fate.
“Our bones have a limited pool of stem cells to draw from to create new bone. If we could coax these cells toward a bone cell fate and away from fat, it would be a great advancement in our ability to promote bone health and healing.”
Dr. Aaron James
The investigators conducted their research in a rat model as well as in human cell cultures, and they report their findings in the journal Scientific Reports.
The protein that drives cell fate
Previous studies that Dr. James conducted have suggested that a particular signaling protein called WISP-1 is likely to drive the fate of perivascular stem cells by “telling” them whether to form fat or bone tissue.
In the current study, the researchers sought to prove WISP-1’s role in determining stem cell fate by genetically modifying a set of human stem cells to stop them from producing this protein.
When they compared gene activity in the engineered stem cells with gene activity in cells that still produced WISP-1, the researchers confirmed that the protein played an important role. In the cells without WISP-1, four of the genes responsible for fat formation had a 50–200 percent higher level of activity than they did in the cells continuing to produce WISP-1.
This also indicated that the correct dosage of this signaling protein could drive the stem cells to form bone tissue instead of fat tissue.
As expected, when the researchers then modified stem cells to increase WISP-1 production, they noticed that three of the genes that stimulate bone tissue growth became twice as active compared with those in stem cells with normal levels of the signaling protein.
At the same time, the activity of genes that stimulated the growth of fat tissue — such as peroxisome proliferator-activated receptor gamma (PPARG) — was 42 percent lower in stem cells with a WISP-1 boost, and this decrease occurred in favor of genes that determine bone tissue growth.
Stem cell intervention shows promise
In the next stage of the study, the scientists used a rat model to determine whether WISP-1 could boost bone healing in spinal fusion, a type of medical intervention that requires joining two or more vertebrae (spine bones) to form a single bone.
The therapeutic use of spinal fusion is to improve back pain or spinal stability in the context of various conditions that affect the spine, such as scoliosis.
Usually, “Such a procedure requires a massive amount of new bone cells,” explains Dr. James. “If we could direct bone cell creation at the site of the fusion, we could help patients recover more quickly and reduce the risk of complications,” he notes.
In the current study, the researchers injected human stem cells that had active WISP-1 into rats. They did this between the vertebrae that were due to become joined as part of the fusion procedure.
After 4 weeks, Dr. James and his team found that the animals still displayed high levels of WISP-1 in their spinal tissue. Moreover, new bone tissue was already forming in the right places, allowing the vertebrae to become “welded.”
Conversely, rats that had received the same surgical intervention but without the WISP-1 boost did not present any vertebral fusion during this same period.
“We hope our findings will advance the development of cellular therapies to promote bone formation after surgeries like this one and for other skeletal injuries and diseases, such as broken bones and osteoporosis,” Dr. James declares.
In the future, the research team also aims to find out whether reducing WISP-1 levels in stem cells could lead them to form fat tissue, which could help promote faster wound healing.
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