美国南加州大学陈健夫、柴洋团队合作发现，颅骨祖细胞(SPCs)驱动的脑膜淋巴修复可改善颅缝早闭患者的神经认知功能。相关论文于2023年10月19日发表于国际顶尖学术期刊《细胞—干细胞》杂志上。

他们发现脑膜淋巴管和脑灌注受损驱动Twist1+/−小鼠的神经认知缺陷，Twist1+/−是一种颅缝闭锁重现人类Saethre-Chotzen综合征的动物模型。SPCs缺失导致颅骨畸形和颅内压升高，而将SPCs移植回突变小鼠可通过两种机制减轻淋巴和脑缺陷：(1)通过颅骨矫正降低升高的颅内压;(2)通过SPCs分泌的血管内皮生长因子-C(VEGF-C)促进淋巴内皮细胞(LECs)的生长和迁移。

用VEGF-C治疗Twist1+/−小鼠可促进脑膜淋巴生长，修复ICP、脑灌注和神经认知功能缺陷。因此，颅骨通过脑膜淋巴管与大脑在功能上整合，脑膜淋巴管在颅缝闭锁中受损，可以通过VEGF-C激活SPC驱动的淋巴管来恢复。

据悉，脑膜位于颅骨和大脑的交界面，是淋巴血管和SPC的所在地。头骨和大脑的交流方式在很大程度上仍然未知。

附：英文原文

Title: Skull progenitor cell-driven meningeal lymphatic restoration improves neurocognitive functions in craniosynostosis

Author: Li Ma, Qing Chang, Fei Pei, Mengmeng Liu, Wei Zhang, Young-Kwon Hong, Yang Chai, Jian-Fu Chen

Issue&Volume: 2023-10-19

Abstract: The meninges lie in the interface between the skull and brain, harboring lymphatic vasculature and skull progenitor cells (SPCs). How the skull and brain communicate remains largely unknown. We found that impaired meningeal lymphatics and brain perfusion drive neurocognitive defects in Twist1+/ mice, an animal model of craniosynostosis recapitulating human Saethre-Chotzen syndrome. Loss of SPCs leads to skull deformities and elevated intracranial pressure (ICP), whereas transplanting SPCs back into mutant mice mitigates lymphatic and brain defects through two mechanisms: (1) decreasing elevated ICP by skull correction and (2) promoting the growth and migration of lymphatic endothelial cells (LECs) via SPC-secreted vascular endothelial growth factor-C (VEGF-C). Treating Twist1+/ mice with VEGF-C promotes meningeal lymphatic growth and rescues defects in ICP, brain perfusion, and neurocognitive functions. Thus, the skull functionally integrates with the brain via meningeal lymphatics, which is impaired in craniosynostosis and can be restored by SPC-driven lymphatic activation via VEGF-C.

DOI: 10.1016/j.stem.2023.09.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00359-4