A neurospheroid network-stamping method for neural transplantation to the brain
A neurospheroid network-stamping method for neural transplantation to the brain
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DOI：
10.1016/j.biomaterials.2010.08.008
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发表时间：
2010-12-01
期刊：
影响因子：
14
通讯作者：
Takeuchi, Shoji
中科院分区：
文献类型：
--
作者：
Kato-Negishi, Midori;Tsuda, Yukiko;Takeuchi, Shoji
利用神经干细胞的神经移植疗法已被认为是神经退行性疾病的潜在治疗方法。事实上，这种疗法被认为是有效的替代退化的神经元在有限的解剖区域。然而，由于注射的神经干细胞随机整合到宿主神经网络中，因此需要另一种方法来建立大脑选择区域之间的神经通路或治疗多个大脑区域的广泛变性。利用组织工程技术在体外构建神经网络是一种很有前途的治疗方法。在这项研究中，我们设计了一个三维（3D）组织与神经元网络，可以很容易地操纵和移植到宿主脑组织在体内。聚二甲基硅氧烷微室阵列促进了多个神经球体的形成，这些神经球体又通过神经元突起相互连接，形成厘米大小的神经球体网络（NSN）。NSN可转移到大脑皮质表面，而不损伤神经网络。移植到皮层组织后，NSN显示神经活动超过8天。此外，移植NSN的神经元将其轴突延伸到宿主皮层组织中，并与宿主神经元建立突触连接。我们的研究结果表明，这种方法可以为治疗严重的退行性脑疾病奠定基础。(C)2010爱思唯尔有限公司版权所有。
Neural transplantation therapy using neural stem cells has received as potential treatments for neurode-generative diseases. Indeed, this therapy is thought to be effective for replacement of degenerating neurons in restricted anatomical region. However, because injected neural stem cells integrate randomly into the host neural network, another approach is needed to establish a neural pathway between selective areas of the brain or treat widespread degeneration across multiple brain regions. One of the promising approaches might be a therapy using pre-made neural network in vitro by the tissue engineering technique. In this study, we engineered a three-dimensional (3D) tissue with a neuronal network that can be easily manipulated and transplanted onto the host brain tissue in vivo. A polydimethylsiloxane microchamber array facilitated the formation of multiple neurospheroids, which in turn interconnected via neuronal processes to form a centimeter-sized neurospheroid network (NSN). The NSN was transferable onto the cortical surface of the brain without damage of the neuronal network. After transfer onto the cortical tissue, the NSN showed neural activity for more than 8 days. Moreover, neurons of the transplanted NSN extended their axons into the host cortical tissue and established synaptic connections with host neurons. Our findings suggest that this method could lay the foundation for treating severe degenerative brain disease. (C) 2010 Elsevier Ltd. All rights reserved.