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In Vivo
Dental Research
Cell Therapy for Congenital
Craniofacial Deformity Shows Success
Team led by College of Dental Medicine researcher uses stem
cells to grow new tissue


One in every 2,500 babies born each year is affected by a craniofacial deformity known as craniosynostosis. This condition develops prenatally, when one or more of the fibrous joints between the bones of the skull – called the cranial sutures – close prematurely, before brain growth is complete. As a result, the brain can’t grow into its natural shape and compensates by growing into other areas of the skull. Children with craniosynostosis can develop microcephaly or hydrocephalus, developmental delays, mental retardation, seizures, and blindness.
      Usually, children with craniosynostosis undergo surgery once they are several months old in order to separate the fused sutures and reshape the skull.
This surgery can be painful and extensive, involving a multispecialty team including neurosurgeons and plastic surgeons; sometimes it must be repeated if the sutures re-fuse. Now, a new cell-based therapy developed by Jeremy Mao, D.D.S., Ph.D., professor of dental medicine, and colleagues offers hope for a much simpler, less painful craniosynostosis repair.
      “Currently, surgeons lift the entire top of the skull, like half a soccer ball, then cut out the synostosed cranial suture and reshape the rest of the other bones, like a jigsaw puzzle,” says Dr. Mao. “It’s extremely complicated, very costly, and involves considerable trauma for the child and the family. Our goal was to see if this level of surgical trauma could be reduced, from working on all the skull bones to just the localized area.”
      Working in a rat model, Dr. Mao and his colleagues used autologous mesenchymal stem cells to create and graft a new cranial suture. After the cells were harvested from the rats, they were manipulated over the course of two to three weeks, and then the graft was implanted at the same time surgery was performed.
      The approach proved successful in the rats, the first time a regenerated cranial suture from autologous stem cells was used to replace a synostosed cranial suture in an in vivo model. “Because a cranial suture is created from the stem cells, it continues to grow with the patient, without leading to secondary synostosis,” Dr. Mao says.
      Dr. Mao is optimistic about the procedure’s success in human trials, since two key elements – the autologous stem cells and the carrier for the cells, a collagen sponge such as those used daily in operating rooms – are already very well understood. “Because we don’t need to use foreign tissue, conceptually this could be replicated in human patients,” he says.
      But not immediately. The long-term outcomes in the rats must be observed before human studies can begin. “We need to observe how the cranial suture works in the rats over time,” Dr. Mao says. (In a rat’s lifespan, long term means months.) “But we are cautiously optimistic that this option will be available to patients.”


Stem Cells Repair Cranial Defect
Adult stem cells were isolated from bone marrow via minimally invasive approach
Adult stem cells were isolated from bone marrow via minimally invasive approach
(a) They were multiplied (b,c) A small protein, TGFb3, was wrapped in a biomaterial in small spheres (d) Cells and spheres were placed in collagen sponges that are used in operating rooms. These grafts were implanted to replace a fused cranial suture in the rat.


—Gina Shaw

Illustration by Nancy Heim

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