Salaris Federico, Colosi Cristina, Brighi Carlo, Soloperto Alessandro, Turris Valeria de, Benedetti Maria Cristina, Ghirga Silvia, Rosito Maria, Di Angelantonio Silvia, Rosa Alessandro
Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
J Clin Med. 2019 Oct 2;8(10):1595. doi: 10.3390/jcm8101595.
Bioprinting techniques use bioinks made of biocompatible non-living materials and cells to build 3D constructs in a controlled manner and with micrometric resolution. 3D bioprinted structures representative of several human tissues have been recently produced using cells derived by differentiation of induced pluripotent stem cells (iPSCs). Human iPSCs can be differentiated in a wide range of neurons and glia, providing an ideal tool for modeling the human nervous system. Here we report a neural construct generated by 3D bioprinting of cortical neurons and glial precursors derived from human iPSCs. We show that the extrusion-based printing process does not impair cell viability in the short and long term. Bioprinted cells can be further differentiated within the construct and properly express neuronal and astrocytic markers. Functional analysis of 3D bioprinted cells highlights an early stage of maturation and the establishment of early network activity behaviors. This work lays the basis for generating more complex and faithful 3D models of the human nervous systems by bioprinting neural cells derived from iPSCs.
生物打印技术使用由生物相容性非生物材料和细胞制成的生物墨水，以可控方式并具有微米级分辨率构建三维结构。最近，利用诱导多能干细胞（iPSC）分化产生的细胞，制造出了代表几种人体组织的三维生物打印结构。人类iPSC可以分化为多种神经元和神经胶质细胞，为构建人类神经系统模型提供了理想工具。在此，我们报告一种通过对源自人类iPSC的皮质神经元和神经胶质前体细胞进行三维生物打印而生成的神经结构。我们表明，基于挤压的打印过程在短期和长期内均不会损害细胞活力。生物打印的细胞可以在构建体内进一步分化，并正确表达神经元和星形胶质细胞标志物。对三维生物打印细胞的功能分析突出了其成熟的早期阶段以及早期网络活动行为的建立。这项工作为通过生物打印源自iPSC的神经细胞来生成更复杂、更逼真的人类神经系统三维模型奠定了基础。
