If you grew up during the 90’s, you most certainly will remember the famous “Got Milk?” advertising campaign to boost milk consumption. The plug was that milk was an invaluable source of calcium, a mineral that’s essential for growing strong bones. Drinking three glasses of the white stuff a day, supposedly would help deter osteoporosis, or the weakening and loss of bone with old age.
Research has proven that calcium is essential for growing and maintaining healthy bones. But milk isn’t the only source of calcium in the human diet, and a diet rich in calcium alone won’t prevent everyone from experiencing some amount of bone loss as they grow older. It also won’t help patients who suffer from bone skeletal defects grow new bone.
So whatever are we to do about bone loss and bone abnormalities? Here, we tell the “Tale of two stem cell treatments” where scientists tackle these problems using stem cell-derived therapies.
Protein Combo Boosts Bone Growth
Our first story comes from a CIRM-funded team of UCLA scientists. This team is interested in developing a better therapy to treat bone defects and osteoporosis. The current treatment for bone loss is an FDA-approved bone regenerating therapy involving the protein BMP-2 (bone morphogenetic protein-2). The problem with BMP-2 is that it can cause serious side effects when given in high doses. Two of the major ones are abnormal bone growth and also making stem cells turn into fat cells as well as bone cells.
The UCLA group attempted to improve the BMP-2 treatment by adding a second protein called NELL-1 (which they knew was good at stimulating bone growth from previous studies). The combination of BMP-2 and NELL-1 resulted in bone growth and also prevented stem cells from making fat cells.
Upon further exploration, they found that NELL-1 acts as a signaling switch that controls whether a stem cell becomes a bone cell or a fat cell. Thus, with NELL-1 present, BMP-2 can only turn stem cells into bone cells.
Kang Ting, a lead author on the study, explained the significance of their new strategy to improve bone regeneration in a UCLA press release:
“Before this study, large bone defects in patients were difficult to treat with BMP2 or other existing products available to surgeons. The combination of NELL-1 and BMP2 resulted in improved safety and efficacy of bone regeneration in animal models — and may, one day, offer patients significantly better bone healing.”
Chia Soo, another lead author on the study, emphasized the importance of using NELL-1 in combination with BMP-2:
“In contrast to BMP2, the novel ability of NELL-1 to stimulate bone growth and repress the formation of fat may highlight new treatment approaches for osteoporosis and other therapies for bone loss.”
Stem cells that could fix deformed skulls
Our second story comes from a group at the University of Rochester. Their goal is to repair bones in the face and skull of patients suffering from congenital deformities, or damage due to injury or cancer surgery.
In a report published in Nature Communications, the scientists identified a population of skeletal stem cells that orchestrate the formation of the skull and can promote craniofacial bone repair in mice.
They identified this special population of skeletal stem cells by their expression of a protein called Axin2. Genetic mutations in the Axin2 gene can cause a birth defect called craniosynostosis. This condition causes the bone plates of a baby’s skull to fuse too early, causing skull deformities and impaired brain development.
According to a news release from the University of Rochester, the group’s “latest evidence shows that stem cells central to skull formation are contained within Axin2 cell populations, comprising about 1 percent—and that the lab tests used to uncover the skeletal stem cells might also be useful to find bone diseases caused by stem cell abnormalities.”
Additionally, senior author on the study, Wei Hsu, “believes his findings contributee to an emerging field involving tissue engineering that uses stem cells and other materials to invent superior ways to replace damaged craniofacial bones in humans due to congenital disease, trauma, or cancer surgery.”
Two different studies, one common goal
Both studies have a common goal: to repair or regenerate bone to treat bone loss, damage, or deformities. I can’t help but wonder whether these different strategies could be combined in a way to that would bring more benefit to the patient than using either strategy alone.
Could we use BMP-2 and NELL-1 treatment along with Axin2 skeletal stem cells to treat craniosynostosis or repair damaged skulls? Or could we identify new stem cell populations in bone that would help patients suffering from osteoporosis?
I’m sure scientists will answer these questions sooner rather than later, and when they do, you’ll be sure to read about it on the Stem Cellar!