Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds.
Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds.
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DOI：
10.1038/ncomms10862
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发表时间：
2016-03-17
影响因子：
16.6
通讯作者：
Moghe PV
中科院分区：
文献类型：
--
作者：
Carlson AL;Bennett NK;Francis NL;Halikere A;Clarke S;Moore JC;Hart RP;Paradiso K;Wernig M;Kohn J;Pang ZP;Moghe PV
用人多能干细胞衍生的神经元进行细胞替代疗法具有改善神经退行性功能障碍和中枢神经系统损伤的潜力，但是重编程的神经元在移植期间解离和空间紊乱，导致体内细胞存活、功能和植入不良。在这里，我们提出了三维（3D）microtopographic支架的设计，使用可调的电纺微纤维聚合物基板，促进原位干细胞神经元重编程，神经网络的建立和支持神经元植入大脑。支架支持的，重编程的神经元网络被成功移植到器官型海马脑切片，显示出相对于注射的分离细胞，神经突生长和动作电位放电增加了1.35倍的改善。将支架支持的神经元网络移植到小鼠脑纹状体中，相对于注射的分离细胞，注射部位的存活率提高了38倍，并允许递送多种神经元亚型。因此，3D微尺度生物材料代表了具有广泛神经再生相关性的治疗性人类神经元移植的有希望的平台。 人类多能干细胞衍生的神经元具有用于脑损伤和疾病的细胞替代疗法的潜力，但需要克服移植问题。在这里，作者使用微地形支架将神经元移植到海马类器官和小鼠大脑纹状体中。
Cell replacement therapy with human pluripotent stem cell-derived neurons has the potential to ameliorate neurodegenerative dysfunction and central nervous system injuries, but reprogrammed neurons are dissociated and spatially disorganized during transplantation, rendering poor cell survival, functionality and engraftment in vivo. Here, we present the design of three-dimensional (3D) microtopographic scaffolds, using tunable electrospun microfibrous polymeric substrates that promote in situ stem cell neuronal reprogramming, neural network establishment and support neuronal engraftment into the brain. Scaffold-supported, reprogrammed neuronal networks were successfully grafted into organotypic hippocampal brain slices, showing an ∼3.5-fold improvement in neurite outgrowth and increased action potential firing relative to injected isolated cells. Transplantation of scaffold-supported neuronal networks into mouse brain striatum improved survival ∼38-fold at the injection site relative to injected isolated cells, and allowed delivery of multiple neuronal subtypes. Thus, 3D microscale biomaterials represent a promising platform for the transplantation of therapeutic human neurons with broad neuro-regenerative relevance. Human pluripotent stem cell derived neurons have the potential for cell replacement therapy for brain injury and disease but problems on transplantation need to be overcome. Here, the authors use a microtopographic scaffold to graft neurons into both hippocampal organoids and the mouse brain striatum.