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结构对准引导内源性神经干细胞的定向迁移和分化,用于治疗脑损伤中的神经发生。

Structural alignment guides oriented migration and differentiation of endogenous neural stem cells for neurogenesis in brain injury treatment.

机构信息

State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Department of Neurosurgery, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 100040, China; Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai, 200127, China.

Department of orthopacdic III, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.

出版信息

Biomaterials. 2022 Jan;280:121310. doi: 10.1016/j.biomaterials.2021.121310. Epub 2021 Dec 3.

DOI:10.1016/j.biomaterials.2021.121310
PMID:34890972
Abstract

Radial glia (RG) cells that align in parallel in the embryonic brain are found to be able to guide the directed migration of neurons in response to brain injury. Therefore, biomaterials with aligned architectures are supposed to have positive effects on neural migration and neurogenic differentiation for brain injury repair that are rarely addressed, although they have been widely demonstrated in spinal cord and peripheral nerve system. Here, we present a highly biomimetic scaffold of aligned fibrin hydrogel (AFG) that mimics the oriented structure of RG fibers. Through a combination of histological, behavioral, imaging, and transcriptomic analyses, we demonstrated that transplanting the AFG scaffold into injured cortical brains promotes effective migration, differentiation, and maturation of endogenous neural stem cells, resulting in neurological functional recovery. Therefore, this study will light up a new perspective on applying an aligned scaffold to promote cortical regeneration after injury by inducing endogenous neurogenesis.

摘要

在胚胎大脑中排列成平行的放射状胶质 (RG) 细胞被发现能够引导神经元的定向迁移,以响应脑损伤。因此,具有定向结构的生物材料应该对脑损伤修复中的神经迁移和神经发生分化有积极影响,但尽管它们在脊髓和周围神经系统中得到了广泛的证明,却很少被关注到。在这里,我们展示了一种高度仿生的纤维蛋白水凝胶(AFG)的定向支架,它模拟了 RG 纤维的定向结构。通过组织学、行为学、成像和转录组学分析的结合,我们证明了将 AFG 支架移植到受损的皮质脑内可以促进内源性神经干细胞的有效迁移、分化和成熟,从而实现神经功能的恢复。因此,这项研究将为通过诱导内源性神经发生来促进损伤后皮质再生提供一个新的应用定向支架的视角。

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