3D Bioprinting Human Induced Pluripotent Stem Cell-Derived Neural Tissues Using a Novel Lab-on-a-Printer Technology
3D Bioprinting Human Induced Pluripotent Stem Cell-Derived Neural Tissues Using a Novel Lab-on-a-Printer Technology
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DOI：
10.3390/app8122414
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发表时间：
2018-12-01
影响因子：
2.7
通讯作者：
Willerth, Stephanie M.
中科院分区：
文献类型：
--
作者：
de la Vega, Laura;Rosas Gomez, Diego A.;Willerth, Stephanie M.
大多数神经系统疾病和障碍缺乏真正的治疗方法，包括脊髓损伤（SCI）。因此，目前的治疗仅减轻这些神经疾病和病症的症状。源自人类诱导多能干细胞（hiPSC）的工程神经组织可以作为鉴定治疗此类疾病和病症的药物靶点的有力工具。在这项工作中，我们展示了hiPSC衍生的神经祖细胞（NPC）如何使用Aspect Biosystems的新型RX 1生物打印机结合我们独特的基于纤维蛋白的生物墨水快速生物打印成定义的结构，因为打印四种组织需要不到5分钟。与不太复杂的生物打印方法相比，这种打印过程保留了高水平的细胞活力（>81%）及其分化能力。这些生物打印的神经组织在培养15天后表达神经元标志物β T-III（45 +/-20.9%），并且表达与脊髓（SC）运动神经元（MN）相关的标志物，例如Olig 2（68.8 +/-6.9%）和HB 9（99.6 +/-4%），如流式细胞术所示。如免疫细胞化学所示，生物打印的神经组织在培养30天后表达成熟的MN标志物ChaT。总之，我们提出了一种新的方法，用于高通量生产成熟的hiPSC衍生的神经组织，其具有与SC中发现的结构相似的确定结构。
Most neurological diseases and disorders lack true cures, including spinal cord injury (SCI). Accordingly, current treatments only alleviate the symptoms of these neurological diseases and disorders. Engineered neural tissues derived from human induced pluripotent stem cells (hiPSCs) can serve as powerful tools to identify drug targets for treating such diseases and disorders. In this work, we demonstrate how hiPSC-derived neural progenitor cells (NPCs) can be bioprinted into defined structures using Aspect Biosystems' novel RX1 bioprinter in combination with our unique fibrin-based bioink in rapid fashion as it takes under 5 min to print four tissues. This printing process preserves high levels of cell viability (>81%) and their differentiation capacity in comparison to less sophisticated bioprinting methods. These bioprinted neural tissues expressed the neuronal marker, beta T-III (45 +/- 20.9%), after 15 days of culture and markers associated with spinal cord (SC) motor neurons (MNs), such as Olig2 (68.8 +/- 6.9%), and HB9 (99.6 0 +/-.4%) as indicated by flow cytometry. The bioprinted neural tissues expressed the mature MN marker, ChaT, after 30 days of culture as indicated by immunocytochemistry. In conclusion, we have presented a novel method for high throughput production of mature hiPSC-derived neural tissues with defined structures that resemble those found in the SC.