Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis

Yu, Mengfei; Ma, Li; Yuan, Yuan; Ye, Xin; Montagne, Axel; He, Jinzhi; Ho, Thach-Vu; Wu, Yingxi; Zhao, Zhen; Maria, Naomi Sta; Jacobs, Russell E.; Urata, Mark M.; Wang, Huiming; Zloković, Berislav V.; Chen, Jianfu; Chai, Yang

doi:10.1016/j.cell.2020.11.037

Cited by 99 publications

(108 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transplantation of skeletal stem/progenitor cells with Wnt3a led to patency of the craniosynostotic suture following its ablation, which may be due to suture mesenchyme reconstitution or indeed arise as a result of failure of healing of the bone defect. Our findings are supported by a recent study 58 , showing that Gli-1 + MSCs transplantation into a surgically ablated Twist-1 +/− craniosynostotic suture prevented resynostosis, however, cWnt stimulation was not required. This difference could reflect ongoing autocrine cWnt signaling in Gli-1 + MSCs, however, this remains a hypothesis.…”

Section: Discussionsupporting

confidence: 89%

Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis

et al. 2021

View full text Add to dashboard Cite

Cranial sutures are major growth centers for the calvarial vault, and their premature fusion leads to a pathologic condition called craniosynostosis. This study investigates whether skeletal stem/progenitor cells are resident in the cranial sutures. Prospective isolation by FACS identifies this population with a significant difference in spatio-temporal representation between fusing versus patent sutures. Transcriptomic analysis highlights a distinct signature in cells derived from the physiological closing PF suture, and scRNA sequencing identifies transcriptional heterogeneity among sutures. Wnt-signaling activation increases skeletal stem/progenitor cells in sutures, whereas its inhibition decreases. Crossing Axin2LacZ/+ mouse, endowing enhanced Wnt activation, to a Twist1+/− mouse model of coronal craniosynostosis enriches skeletal stem/progenitor cells in sutures restoring patency. Co-transplantation of these cells with Wnt3a prevents resynostosis following suturectomy in Twist1+/− mice. Our study reveals that decrease and/or imbalance of skeletal stem/progenitor cells representation within sutures may underlie craniosynostosis. These findings have translational implications toward therapeutic approaches for craniosynostosis.

show abstract

Section: Discussionsupporting

confidence: 89%

Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Of note, a scRNAseq study of the developing mouse cranial suture indicate that outer periosteal dural fibroblasts and inner dural border fibroblasts are likely molecularly distinct fibroblast populations (Farmer et al, 2021). Additionally, dural fibroblasts have been shown to play a role in suture patency during calvarium expansion to accommodate brain growth (Cooper et al, 2012;Yu et al, 2021).…”

Section: Fibroblastsmentioning

confidence: 99%

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Derk

Jones

Como

et al. 2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The meninges are the fibrous covering of the central nervous system (CNS) which contain vastly heterogeneous cell types within its three layers (dura, arachnoid, and pia). The dural compartment of the meninges, closest to the skull, is predominantly composed of fibroblasts, but also includes fenestrated blood vasculature, an elaborate lymphatic system, as well as immune cells which are distinct from the CNS. Segregating the outer and inner meningeal compartments is the epithelial-like arachnoid barrier cells, connected by tight and adherens junctions, which regulate the movement of pathogens, molecules, and cells into and out of the cerebral spinal fluid (CSF) and brain parenchyma. Most proximate to the brain is the collagen and basement membrane-rich pia matter that abuts the glial limitans and has recently be shown to have regional heterogeneity within the developing mouse brain. While the meninges were historically seen as a purely structural support for the CNS and protection from trauma, the emerging view of the meninges is as an essential interface between the CNS and the periphery, critical to brain development, required for brain homeostasis, and involved in a variety of diseases. In this review, we will summarize what is known regarding the development, specification, and maturation of the meninges during homeostatic conditions and discuss the rapidly emerging evidence that specific meningeal cell compartments play differential and important roles in the pathophysiology of a myriad of diseases including: multiple sclerosis, dementia, stroke, viral/bacterial meningitis, traumatic brain injury, and cancer. We will conclude with a list of major questions and mechanisms that remain unknown, the study of which represent new, future directions for the field of meninges biology.

show abstract

“…The Authors showed that loss of Gli1 + MSCs induces premature coronal suture fusion in Twist1 +/− mice, confirming that this subpopulation of MSC are largely required for craniofacial bone turnover, homeostasis and repair [110]. They also showed that the implantation of MSC-graft leads to suture regeneration by restoring Gli1 + cells subpopulation within cranial suture both through exogenously implanted Gli1+ MSCs and endogenous MSCs derived from the dura mater [108]. Our group has indeed recently demonstrated that GLI1 represents a specific marker for MSC in the human calvarial niche [21].…”

Section: Tissue Engineering Strategiesmentioning

confidence: 89%

“…A recent study lead by Yu et al, demonstrated the efficacy to restore coronal suture patency in a Twist1 +/− mice Model using Gli1 + MSCs combined with methacrylated gelatin (GelMA) modified with Matrigel and collagen I (COL-I) [108]. GelMA (M-GM) scaffold is highly biocompatible and biodegradable, and it easily adapts to defects [109].…”

Section: Tissue Engineering Strategiesmentioning

confidence: 99%

Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis

et al. 2021

View full text Add to dashboard Cite

Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to the premature fusion of skull sutures. CS care requires surgical treatment of variable complexity, aimed at resolving functional and cosmetic defects resulting from the skull growth constrain. Despite significant innovation in the management of CS, morbidity and mortality still exist. Residual cranial defects represent a potential complication and needdedicated management to drive a targeted bone regeneration while modulating suture ossification. To this aim, existing techniques are rapidly evolving and include the implementation of novel biomaterials, 3D printing and additive manufacturing techniques, and advanced therapies based on tissue engineering. This review aims at providing an exhaustive and up-to-date overview of the strategies in use to correct these congenital defects, focusing on the technological advances in the fields of biomaterials and tissue engineering implemented in pediatric surgical skull reconstruction, i.e., biodegradable bone fixation systems, biomimetic scaffolds, drug delivery systems, and cell-based approaches.

show abstract

Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis

Cited by 99 publications

References 66 publications

Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis

Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis

Contact Info

Product

Resources

About