心脏是人胚胎发育的第一个器官，先天性心脏相关疾病的发病率长期以来居高不下对众多新生儿家庭造成巨大困扰。美国FDA要求所有药物必须注明对孕妇以及婴儿的潜在健康危险，但一些药物标签上只注明了其在动物水平的检测中没有发现致病风险，但还没有在孕妇群体中进行深入研究。
组织器官3D模型是药物开发、评价药物副作用和模拟组织器官早期发育的重要工具。近日，有研究人员基于生物材料以及诱导多能干细胞技术，建立了心脏的3D组织模型，该模型能够模拟人类心脏的早期发育阶段。通过在组织培养皿中加入一层多聚物，以及在其表面蚀刻形成微小的痕迹，细胞能够与这些痕迹牢固地结合。由于干细胞本身并不会粘附在多聚物上，因此它们能够沿着蚀刻痕迹生长，并最终发育形成3D结构。研究人员Zhen Ma表示，该技术实现了利用干细胞分化形成组织，而非利用已经成熟的心脏细胞进行组织重构。相比之下，前者具有更多的分化层，因此能够更好地模拟组织自然过程中的分化情况。
研究人员表示，现在医生们在给孕妇下处方时面临的一大难题是无法确定药物对胚胎发育是否以及会产生何种影响，因为很难针对性地就药物的胚胎发育影响开展临床试验。基于诱导多能干细胞技术的心脏3D模型能够帮助检测多种药物对胚胎的发育影响，从而提高孕妇以及胎儿的健康水平。
推荐阅读原文：
Generation of spatial-patterned early-developing cardiac organoids using human pluripotent stem cells.
The creation of human induced pluripotent stem cells (hiPSCs) has provided an unprecedented opportunity to study tissue morphogenesis and organ development through 'organogenesis-in-a-dish'. Current approaches to cardiac organoid engineering rely on either direct cardiac differentiation from embryoid bodies (EBs) or generation of aligned cardiac tissues from predifferentiated cardiomyocytes from monolayer hiPSCs. To experimentally model early cardiac organogenesis in vitro, our protocol combines biomaterials-based cell patterning with stem cell organoid engineering. 3D cardiac microchambers are created from 2D hiPSC colonies; these microchambers approximate an early-development heart with distinct spatial organization and self-assembly. With proper training in photolithography microfabrication, maintenance of human pluripotent stem cells, and cardiac differentiation, a graduate student with guidance will likely be able to carry out this experimental protocol, which requires 3 weeks. We envisage that this in vitro model of human early heart development could serve as an embryotoxicity screening assay in drug discovery, regulation, and prescription for healthy fetal development. We anticipate that, when applied to hiPSC lines derived from patients with inherited diseases, this protocol can be used to study the disease mechanisms of cardiac malformations at an early stage of embryogenesis.
