Calvarial Suture-Derived Stem Cells and Their Contribution to Cranial Bone Repair

Abstract

In addition to the natural turnover during life, the bones in the skeleton possess the ability to self-repair in response to injury or disease-related bone loss. Based on studies of bone defect models, both processes are largely supported by resident stem cells. In the long bones, the source of skeletal stem cells has been widely investigated over the years, where the major stem cell population is thought to reside in the perivascular niche of the bone marrow. In contrast, we have very limited knowledge about the stem cells contributing to the repair of calvarial bones. In fact, until recently, the presence of specific stem cells in adult craniofacial bones was uncertain. These flat bones are mainly formed via intramembranous rather than endochondral ossification and thus contain minimal bone marrow space. It has been previously proposed that the overlying periosteum and underlying dura mater provide osteoprogenitors for calvarial bone repair. Nonetheless, recent studies have identified a major stem cell population within the suture mesenchyme with multiple differentiation abilities and intrinsic reparative potential. Here we provide an updated review of calvarial stem cells and potential mechanisms of regulation in the context of skull injury repair.

The Osteogenic Potential of the Neural Crest Lineage May Contribute to Craniosynostosis

“…This might reflect an expected delay in the differentiation stage, given that a proportion of the sutural mesenchyme is still uncommitted when harvested from the explants, whereas the cells harvested from the bone chips are likely fully differentiated at this postnatal stage. While it is true that the sutural mesenchyme harbours numerous undifferentiated stem cells with multi-lineage potential [for review, see Doro et al, 2017], it is possible that, in vitro , these cells require exogenous signalling input to undergo osteogenesis. In addition, it would be interesting to know the dura mater requirements for ossification of the sutural cells.…”

The osteogenic potential of the neural crest lineage may contribute to craniosynostosis

“…This might reflect an expected delay in the differentiation stage, given that a proportion of the sutural mesenchyme is still uncommitted when harvested from the explants, whereas the cells harvested from the bone chips are likely fully differentiated at this postnatal stage. While it is true that the sutural mesenchyme harbours numerous undifferentiated stem cells with multi-lineage potential (reviewed in 20 ), it is possible that, in vitro , these cells require exogenous signalling input to undergo osteogenesis. In addition, it would be interesting to know the dura mater requirements for ossification of the sutural cells.…”

BMP Signaling in the Development and Regeneration of Cranium Bones and Maintenance of Calvarial Stem Cells

“…Gli1+ cells are detectable throughout the entire periosteum, dura, and suture mesenchyme at birth (Guo et al, 2018), but this pattern gradually becomes undetectable by 1 month postnatal, and Gli1+ cells are not detectable in fontanelles or osteocytes. Gli1+ cells eventually restricted to cranial sutures, including the fused posterior frontal suture, where they remain throughout adulthood (Zhao et al, 2015;Doro et al, 2017). Gli1+ cells can contribute to osteogenic fronts, periosteum, and dura after tamoxifen treatment (Guo et al, 2018; Table 2).…”