Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis.

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Public Summary:
In craniosynostosis, a condition where the bones in a baby's skull fuse too early, researchers have discovered an important breakthrough. The skull's growth is normally guided by special cells called mesenchymal stem cells (MSCs) found in the cranial sutures. When craniosynostosis occurs, it can lead to skull deformities, increased pressure inside the head, and even problems with brain function. However, there hasn't been an effective way to study this condition in animals or develop new treatments. In this study, scientists used mice with a genetic mutation (Twist1+/-) that mimicked craniosynostosis in humans, particularly a condition called Saethre-Chotzen syndrome. These mice displayed increased head pressure and behavioral issues similar to those seen in people with the syndrome. The researchers then used a special biodegradable material combined with MSCs to regenerate a functional cranial suture in the mice. This procedure corrected skull deformities, normalized head pressure, and improved the mice's behavior. Even more exciting, the newly regenerated suture acted as a welcoming environment for the mouse's natural MSCs, which helped maintain healthy skull bone growth and repair. This breakthrough suggests a new approach for treating craniosynostosis by using MSCs to regenerate cranial sutures. It offers hope for reversing the skull and brain-related problems in this condition, potentially improving the lives of those affected by this challenging disease.
Scientific Abstract:
Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1(+/-) mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.