ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
Adv Healthc Mater. 2017 Sep;6(17). doi: 10.1002/adhm.201700175. Epub 2017 May 24.
The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient-specific stem cell-based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self-organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct-write printing of cells for encapsulation, proliferation, and differentiation. Here, such a method, employing a clinically amenable polysaccharide-based bioink, is described as the first example of bioprinting human iPSCs for in situ expansion and sequential differentiation. Specifically, we have extrusion printed the bioink including iPSCs, alginate (Al; 5% weight/volume [w/v]), carboxymethyl-chitosan (5% w/v), and agarose (Ag; 1.5% w/v), crosslinked the bioink in calcium chloride for a stable and porous construct, proliferated the iPSCs within the construct and differentiated the same iPSCs into either EBs comprising cells of three germ lineages-endoderm, ectoderm, and mesoderm, or more homogeneous neural tissues containing functional migrating neurons and neuroglia. This defined, scalable, and versatile platform is envisaged being useful in iPSC research and translation for pharmaceuticals development and regenerative medicine.
从诱导多能干细胞 (iPSC) 中创建 3D 组织的能力有望彻底改变干细胞研究和再生医学，包括个体化、患者特异性基于干细胞的治疗方法。然而，使用 iPSC 进行组织工程的例子很少。它们的培养和分化主要是平面的，用于单层细胞支持或诱导自组织胚胎体 (EB) 和类器官。使用先进的生物材料对 iPSC 进行生物打印有望增强开发 3D 组织的努力，理想情况下包括直接写入打印细胞进行封装、增殖和分化。在这里，描述了这样一种方法，该方法使用临床适用的多糖基生物墨水作为第一个示例，用于原位扩增和顺序分化的人 iPSC 生物打印。具体来说，我们已经挤出打印了包括 iPSC 在内的生物墨水，藻酸盐 (Al; 5%重量/体积 [w/v])、羧甲基壳聚糖 (5% w/v) 和琼脂糖 (Ag; 1.5% w/v)，将生物墨水交联在氯化钙中以形成稳定且多孔的结构，在结构内增殖 iPSC 并将相同的 iPSC 分化为包含三个生殖谱系-内胚层、外胚层和中胚层的 EB，或更同质的包含具有功能迁移神经元和神经胶质的神经组织。这个定义明确、可扩展和通用的平台有望在 iPSC 研究和转化为药物开发和再生医学中发挥作用。
