Brain and spinal cord injury repair by implantation of human neural progenitor cells seeded onto polymer scaffolds.
Brain and spinal cord injury repair by implantation of human neural progenitor cells seeded onto polymer scaffolds.
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DOI：
10.1038/s12276-018-0054-9
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发表时间：
2018-04-20
影响因子：
12.8
通讯作者：
Park KI
中科院分区：
文献类型：
--
作者：
Shin JE;Jung K;Kim M;Hwang K;Lee H;Kim IS;Lee BH;Lee IS;Park KI
缺氧缺血性脑损伤（HI）和脊髓损伤（SCI）导致广泛的组织损失和轴突变性。已经报道了聚合物支架和神经祖细胞（NPC）的组合应用通过神经损伤后的多种作用模式来增强神经修复、保护和再生。本研究探讨了生物桥的修复能力和治疗潜力的人胎脑来源的NPC接种在聚（乙醇酸）为基础的支架植入到新生儿HI脑损伤的梗死腔或半切腔在成人SCI。植入人NPC（hNPC）-支架复合物减少了病变体积，诱导了移植细胞的存活、植入和分化，增加了新血管形成，抑制了胶质瘢痕形成，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。神经束追踪显示hNPC-支架移植物似乎改革了HI脑损伤中两个大脑半球神经元与其靶点之间的连接，并保护了SCI中一些受损的皮质脊髓纤维。最后，与对照组相比，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性疼痛。这些发现表明，随着进一步的研究，这种优化的多学科方法结合hNPC与生物材料支架提供了一个更通用的治疗脑损伤和SCI。植入人类胎儿脑细胞的生物可降解支架可以帮助修复啮齿动物的神经损伤。由韩国首尔延世大学医学院的Kook In Park和Il-Shin Lee领导的一个研究小组制造了一个塑料纤维网，并将其浸泡在神经祖细胞中。在几天的时间里，这些细胞分化成不同类型的脑细胞，包括神经元和神经胶质。研究人员将这些细胞支架复合物植入两种啮齿动物模型的损伤部位：新生小鼠大脑缺氧，成年大鼠脊髓切断。在这两种情况下，治疗有助于受伤组织愈合，并改善动物的神经或运动功能。作者认为，这些组织工程结构也可以帮助大脑或脊柱受伤的人。
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. Biodegradable scaffolds seeded with human fetal brain cells can help repair neurological injuries in rodents. A team led by Kook In Park and Il-Shin Lee from the Yonsei University College of Medicine in Seoul, South Korea, created a mesh of plastic fibers that they bathed in neural progenitor cells. Over the course of several days, these cells differentiated into different types of brain cells, including neurons and glia. The researchers implanted these cell-scaffold complexes into the sites of injury in two rodent models: newborn mice with oxygen deprivation to the brain, and adult rats with severed spinal cords. In both cases, the treatment helped the injured tissues heal and improved the neurological or motor function of the animals. The authors suggest these tissue-engineered structures could also help people with brain or spine injuries.