Tissue Models for Neurogenesis and Repair in 3D
Tissue Models for Neurogenesis and Repair in 3D
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DOI：
10.1002/adfm.201803822
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发表时间：
2018-11-28
影响因子：
19
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
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作者：
Grasman, Jonathan M.;Ferreira, Julia A.;Kaplan, David L.
血管和神经组织的发育和成熟在子宫内同时发生，并受到显著串扰的调节。在这里，一个3D组织系统的发展，以模拟神经发生和概括发育信号条件。人脐静脉内皮细胞(HUVECs)种植在胶原凝胶内的通道内，以代表新生血管网络。从鸡背根神经节延伸出来的轴突明显长得更长，并且相对于卸载的通道，更倾向于朝向HUVEC种子通道。为了在没有血管成分的情况下重复这些发现，通道中加载了脑源性神经营养因子(BDNF)，这是HUVEC刺激轴突生长的主要信号分子，轴突也明显延长，与对照组相比，轴突优先向加载BDNF的通道生长。然后将该3D组织系统用作周围神经损伤的体外复制，并在2周内观察神经修复情况。这些结果表明，3D组织系统可以模拟神经网络的形成，可以在撕裂伤后进行修复，并可以用来进一步研究这些网络是如何形成的，以及如何与其他组织相互作用，如皮肤或骨骼肌。
Development and maturation of vascular and neuronal tissues occurs simultaneously in utero, and are regulated by significant crosstalk. Here, the development of a 3D tissue system to model neurogenesis and recapitulate developmental signaling conditions is reported. Human umbilical vein endothelial cells (HUVECs) are seeded inside channels within collagen gels to represent nascent vascular networks. Axons extending from chicken dorsal root ganglia grow significantly longer and preferentially toward the HUVEC seeded channels with respect to unloaded channels. To replicate these findings without the vascular component, channels are loaded with brain-derived neurotrophic factor (BDNF), the principle signaling molecule in HUVEC-stimulated axonal growth, and axons likewise are significantly longer and grow preferentially toward the BDNF-loaded channels with respect to controls. This 3D tissue system is then used as an in vitro replicate for peripheral nerve injury, with neural repair observed within 2 weeks. These results demonstrate that the 3D tissue system can model neural network formation, can repair after laceration injuries, and can be utilized to further study how these networks form and interact with other tissues, such as skin or skeletal muscle.