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These new stem cells can help treat skull malformation in infants - craniosynostosis, and is encouraging as a potential treatment for all skull deformities. Image Credit: TheArtistOfLife.com

Stem cell based birth defect can repair facial bones

Researchers have pinpointed the primary cause of a rare skull disorder in infants, a discovery that could also help wounded soldiers, car-wreck victims and other patients recover from disfiguring facial injuries.

"This has a more implications than we initially thought. We can take advantage of these stem cells not only to repair a birth defect, but to provide facial regeneration for veterans or other people who have suffered traumatic injury."

Yang Chai PhD, lead researcher, the Herman Ostrow School of Dentistry, University of Southern California.

Chai predicted such treatment could be available to patients within the next five to 10 years, providing it shows promise in clinical trials with patients.

"It is a very minimal procedure to just cut off a strip of bone instead of cutting the entire calvaria [skull cap]," Chai added. A stem cell treatment "will truly restore the normal anatomy, which will then be able to respond to the continuous brain growth and the patient can live a normal life."

The team's findings have shifted the scientific perspective on bone disease, according to Hu Zhao, who conducted most of the study's tests on mice.

"Before our findings, people assumed bones all around the body are the same. We are now showing that they are all totally different; that they have a different source of stem cells and a different healing mechanism."

Hu Zhao PhD, Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California.

In their study, the team tracked Gli1+ stem cells that appear within tissues connecting craniofacial bones. They found that a shortage of Gli1+ stem cells hardened the skull and fused the sutures, causing "craniosynostosis," a birth defect that can hinder brain development. So they became curious as to whether Gli1+ stem cells can serve another purpose. They then transplanted the Gli1+ stem cells into injured skull bone areas of mice and within weeks, noticed Gli1+ stem cells were migrating on their own to injured skull areas.

Chai believes the discovery that Gli1+ stem cells assist in bone regeneration indicates doctors will be able to help people who have suffered disfiguring facial injuries in addition to infants diagnosed with craniosynostosis. Using biological treatments instead of multiple high-risk surgeries would be a significant improvement in the quality of life for patients needing help.

Until now, surgeons had unknowingly destroyed regenerative stem cells when operating on craniosynostosis patients. During a typical surgery, doctors break the skull apart to allow for the brain to grow more. Doctors then staple remaining pieces back together and discard unused or damaged bone tissue as waste. However, Gli1+ stem cells are activatied during injury repair. Zhao believes such a procedure actually interferres with healing as Gli1+ stem cells could be lost on the removed bone.

A biological approach would transplant Gli1+ stem cells into targeted areas of skull damage, particularly in infants with craniosynostosis. Growing skull bone would give infants the flexibility needed for their brains to continue to grow normally. For other patients who have suffered head trauma or facial disfigurement due to cancers, the Gli+1 stem cells could help repair fractured or eroded skull areas.

Researchers plan to conduct additional laboratory experiments before the treatment is tested in clinical trials with patients.

The findings were published in this month's issue of the journal Nature Cell Biology.

Abstract
Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial-bone MSCs remain unknown. Here, we identify ?Gli1+ cells within the suture mesenchyme as the main MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. ?Gli1+ cells are typical MSCs in vitro. Ablation of ?Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating that these cells are an indispensable stem cell population. ?Twist1+/− mice with craniosynostosis show reduced ?Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair.

The study was supported by grants to Chai from the National Institute of Dental and Craniofacial Research at the National Institutes of Health.

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