Grasman Jonathan M, Ferreira Julia A, Kaplan David L
Biomedical Engineering Department, Tufts University, Medford, Massachusetts 02155.
Adv Funct Mater. 2018 Nov 28;28(48). doi: 10.1002/adfm.201803822. Epub 2018 Oct 10.
Development and maturation of vascular and neuronal tissues occurs simultaneously in utero, and are regulated by significant crosstalk. We report on the development of a 3D tissue system to model neurogenesis and recapitulate developmental signaling conditions. Human umbilical vein endothelial cells (HUVECs) were seeded inside channels within collagen gels to represent nascent vascular networks. Axons extending from chicken dorsal root ganglia (DRGs) grew significantly longer and preferentially towards the HUVEC seeded channels with respect to unloaded channels. To replicate these findings without the vascular component, channels were loaded with brain-derived neurotrophic factor (BDNF), the principle signaling molecule in HUVEC-stimulated axonal growth, and axons likewise were significantly longer and grew preferentially towards the BDNF-loaded channels with respect to controls. This 3D tissue system was then used as an in vitro replicate for peripheral nerve injury, with neural repair observed within 2 weeks. These results demonstrate that our 3D tissue system can model neural network formation, 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.
血管组织和神经组织的发育与成熟在子宫内同时发生，并受到显著的相互作用调节。我们报告了一种三维组织系统的开发，该系统用于模拟神经发生并重现发育信号条件。将人脐静脉内皮细胞（HUVECs）接种在胶原凝胶内的通道中，以代表新生血管网络。相对于未加载细胞的通道，从鸡背根神经节（DRGs）延伸出的轴突生长得明显更长，并且优先朝着接种了HUVECs的通道生长。为了在没有血管成分的情况下重现这些发现，在通道中加载脑源性神经营养因子（BDNF），这是HUVECs刺激轴突生长的主要信号分子，相对于对照组，轴突同样明显更长，并且优先朝着加载了BDNF的通道生长。然后将这个三维组织系统用作外周神经损伤的体外模型，在两周内观察到了神经修复。这些结果表明，我们的三维组织系统可以模拟神经网络的形成、撕裂伤后的修复，并且可以用于进一步研究这些网络如何形成以及与其他组织（如皮肤或骨骼肌）相互作用。
