Cell: Scientists hope to use stem cell therapy to successfully correct skull and brain function in mouse models of cranial suture early closure, which is expected to be translated into human clinical applications

JANUARY 11, 2021 // -- In a recent study published in the international journal Cell, scientists from the National Institutes of Health and others successfully used stem cells to regenerate parts of the skull, promising to correct the skull shape of young mice with craniosynostosis and reverse their learning and memory impairments.
According to the CDC, one in every 2,500 newborns is affected by early cranial closure, and the only treatment currently is complex surgery within a year of birth, but skull defects usually recur later, and the results of this paper hope to help develop more effective and less invasive treatments for early cranial closure.
Photo Source: Amanda Frataccia, USC researcher Lillian Shum, said the study is a crucial study that demonstrates structural regeneration and functional recovery mechanisms in the brains of animal models of cranial slits;
healthy babies are born with a "sutures" structure, an elastic tissue that fills the space between the skulls, which, in the first few years of life, promotes skull expansion as the brain grows rapidly; In the disease, one or more suture structures enter the bone prematurely, causing gaps between the skull plates to close and trigger abnormal growth of the skull;
Researcher Dr Yang Chai said: 'Scientists have not yet clarified the link between changes in the skull and cognitive impairment in the brain, so we wanted to know if restoring the "stitching" structure could improve the neurocognitive function of the brains of mice carrying key genetic mutations that induce early cranial closure in mice and humans.
the gene, called TWIST1, is thought to be crucial to the formation of "stitched" structures during the development of the body.
in humans, mutations in the gene can trigger Saethre-Chotzen syndrome, a genetic disorder characterized by early cranial closure and other bone dysplative development.
To see if the variable "stitching" structure could be recovered in mice with the Twist1 mutation, the researchers focused on a particular class of stem cells in a healthy succulation structure, which previously showed that the stem cells, called Gli1 plus cells, were critical to maintaining the skull "stitch" structure in young mice.
researchers say that by supplementing the stem cells, they may be able to regenerate flexible "stitching" structures in affected animal bodies.
To test the idea, the researchers added Gli1 plus cells from healthy mouse bodies to biodegradable gels, then placed the mixtures in grooves to reconstruct space at the sutum structure of the skulls of mice with early cranial closure.
Skull imaging and tissue analysis showed that six months later, new fibrous succulation tissue had formed in the area under treatment, and the newly formed tissue remained intact even a year later;
's in-depth analysis showed that Gli1-plus cells in regenerative succutation structures have different origins, some of which are descendants of transplanted cells, while others are animal-owned cells that migrate from nearby regions;
Further studies, the researchers found that untreated mice with early cranial slits increased intracranial stress and performed relatively poorly in social, spatial memory, and exercise learning;
researchers say the stem cell therapy can also reverse the loss of brain capacity and the loss of nerve cells in brain regions involved in learning and memory; studies have revealed the mechanisms behind brain function impairment and the improvement in symptoms of the disease caused by the regeneration of the suture structure.
researcher Chai said: 'I found that the regeneration of the sutum structure based on Gli1 plus stem cells not only restores the shape of the skull, but also improves the neurocognitive function of the brain in the mouse model of early cranial closure.
further work may be needed before testing in humans, including determining the optimal surgical time and the ideal source and level of stem cells.
() Original source: Mengfei Yu, Li Ma, Yuan Yuan, et al. Cranial suture regeneration mitigates skull and neurocognitive defects in craniosynostosis. Cell. Jan. 7, 2021. DOI: 10.1016/j.cell.2020.11.037