Mesenchymal stem cells in tissue homeostasis and regeneration

The human skull is composed of twenty‐two bones connected by sutures, which are fibrous joints that contain skeletal progenitor cells. The calvarial sutures allow compression of the skull during childbirth and dramatic postnatal growth. Craniosynostosis is a common congenital defect characterized by premature suture fusion, which can cause severe outcomes including abnormal growth of the skull, increased intracranial pressure, retarded brain development and impaired neurocongnitive function. Currently, the only treatment option for infants with craniosynostosis is surgery that involves cutting the calvaria into pieces, manually reshaping them, and fixing them in place mechanically, necessitating blood transfusion and complex post‐surgical care. In many cases, the calvarial bones fuse again, which requires repeated operations to relieve the constriction on the brain during the sensitive period of development in order to improve physiological function. Clearly, there is an immense need for a better approach to the treatment of craniosynostosis and prevention of re‐occurrence. Recent studies have shown that Gli1+ cells are an indispensable mesenchymal stem cell (MSC) source within the cranial sutures. Ablation of Gli1+ cells leads to fusion of all craniofacial sutures in adult mice; we have also demonstrated there is a premature loss of Gli1+ cells prior to coronal suture fusion in Twist1 +/ − mice, which provide an important, clinically relevant craniosynostosis model of Saethre‐Chotzen syndrome. Here we took advantage of the Twist1 +/ − mouse model, developed an innovative scaffold combined with Gli1+ MSCs and were able to regenerate a coronal suture and improved the morphology and function of Twist1 +/ − mice. This discovery provides a potential new approach for treating patients with craniosynostosis. Support or Funding Information Supported by the NIDCR, NIH R01 DE026339; U01 DE 026914