美国南加利福尼亚大学颅面分子生物学中心Yang Chai研究组近日取得一项新成果。经过不懈努力，他们的研究发现颅缝再生缓解了颅骨融合症的颅骨和神经认知缺陷。2021年1月7日出版的《细胞》杂志发表了这项成果。
他们显示了具有颅骨突触的Twist1 +/-小鼠具有颅内压升高和神经认知行为异常表型，重现了人类Saethre-Chotzen综合征的特征。使用可生物降解的材料与MSC结合，他们成功地再生了功能性颅骨缝合线，可纠正颅骨畸形，使颅内压正常化并挽救神经认知行为缺陷。再生的缝线创造了一个内生的间充质干细胞（MSC）迁移到的位置，维持了颅骨的稳态和修复。基于MSC的颅骨缝线再生为这种破坏性疾病中的颅骨和神经认知异常逆转提供了治疗模式的转变。
据了解，颅骨融合症是由颅缝线过早融合引起的，颅骨缝线包含MSC，这对颅盖扩张与脑部生长协调至关重要。患有颅骨融合的婴儿具有颅骨畸形、颅内压增高以及并发症，例如损害生活质量的神经认知障碍。缺乏概括这些表型的动物模型，阻碍了迫切需要的创新疗法的发展。
附：英文原文
Title: Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis
Author: Mengfei Yu, Li Ma, Yuan Yuan, Xin Ye, Axel Montagne, Jinzhi He, Thach-Vu Ho, Yingxi Wu, Zhen Zhao, Naomi Sta Maria, Russell Jacobs, Mark Urata, Huiming Wang, Berislav V. Zlokovic, Jian-Fu Chen, Yang Chai
Issue&Volume: 2021/01/07
Abstract: Craniosynostosis results from premature fusion of the cranial suture(s), which containmesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordinationwith brain growth. Infants with craniosynostosis have skull dysmorphology, increasedintracranial pressure, and complications such as neurocognitive impairment that compromisequality of life. Animal models recapitulating these phenotypes are lacking, hamperingdevelopment of urgently needed innovative therapies. Here, we show that Twist1+/ mice with craniosynostosis have increased intracranial pressure and neurocognitivebehavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome.Using a biodegradable material combined with MSCs, we successfully regenerated a functionalcranial suture that corrects skull deformity, normalizes intracranial pressure, andrescues neurocognitive behavior deficits. The regenerated suture creates a niche intowhich endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair.MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverseskull and neurocognitive abnormalities in this devastating disease.
DOI: 10.1016/j.cell.2020.11.037
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31609-3