Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis.
Cell
; 184(1): 243-256.e18, 2021 01 07.
Article
em En
| MEDLINE
| ID: mdl-33417861
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
/
Crânio
/
Cognição
/
Suturas Cranianas
/
Craniossinostoses
Tipo de estudo:
Prognostic_studies
Aspecto:
Patient_preference
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2021
Tipo de documento:
Article