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将人神经祖细胞种植到聚合物支架上,通过植入修复脑和脊髓损伤。

Brain and spinal cord injury repair by implantation of human neural progenitor cells seeded onto polymer scaffolds.

机构信息

Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, 03722, Korea.

Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, Korea.

出版信息

Exp Mol Med. 2018 Apr 20;50(4):1-18. doi: 10.1038/s12276-018-0054-9.

Abstract

Hypoxic-ischemic (HI) brain injury and spinal cord injury (SCI) lead to extensive tissue loss and axonal degeneration. The combined application of the polymer scaffold and neural progenitor cells (NPCs) has been reported to enhance neural repair, protection and regeneration through multiple modes of action following neural injury. This study investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived NPCs seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal HI brain injury or the hemisection cavity in an adult SCI. Implantation of human NPC (hNPC)-scaffold complex reduced the lesion volume, induced survival, engraftment, and differentiation of grafted cells, increased neovascularization, inhibited glial scar formation, altered the microglial/macrophage response, promoted neurite outgrowth and axonal extension within the lesion site, and facilitated the connection of damaged neural circuits. Tract tracing demonstrated that hNPC-scaffold grafts appear to reform the connections between neurons and their targets in both cerebral hemispheres in HI brain injury and protect some injured corticospinal fibers in SCI. Finally, the hNPC-scaffold complex grafts significantly improved motosensory function and attenuated neuropathic pain over that of the controls. These findings suggest that, with further investigation, this optimized multidisciplinary approach of combining hNPCs with biomaterial scaffolds provides a more versatile treatment for brain injury and SCI.

摘要

缺氧缺血性(HI)脑损伤和脊髓损伤(SCI)导致广泛的组织损失和轴突退化。已有报道称,聚合物支架和神经祖细胞(NPCs)的联合应用通过多种作用模式在神经损伤后增强神经修复、保护和再生。本研究探讨了在新生 HI 脑损伤的梗死腔或成年 SCI 的半切腔中植入人胎脑源性 NPC 接种的聚(乙交酯)基支架制成的生物桥的修复能力和治疗潜力。人 NPC(hNPC)-支架复合物的植入减少了病变体积,诱导了移植细胞的存活、植入和分化,增加了新生血管形成,抑制了神经胶质瘢痕形成,改变了小胶质细胞/巨噬细胞反应,促进了病变部位内的神经突生长和轴突延伸,并促进了受损神经回路的连接。示踪研究表明,hNPC-支架移植物似乎在 HI 脑损伤中重建了大脑两个半球中神经元及其靶标之间的连接,并保护了 SCI 中一些受损的皮质脊髓纤维。最后,hNPC-支架复合物移植物显著改善了运动感觉功能,并减轻了神经病理性疼痛,优于对照组。这些发现表明,随着进一步的研究,这种将 hNPCs 与生物材料支架相结合的优化多学科方法为脑损伤和 SCI 提供了更具多功能性的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc73/5938022/508aeb21e957/12276_2018_54_Fig1_HTML.jpg

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