Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing 400030, China.
Exp Neurol. 2021 May;339:113619. doi: 10.1016/j.expneurol.2021.113619. Epub 2021 Jan 23.
Brain organoids are three-dimensional self-assembled structures that are derived from human induced pluripotent stem cells (hiPSCs). They can recapitulate the spatiotemporal organization and function of the brain, presenting a robust system for in vitro modeling of brain development, evolution, and diseases. Significant advances in biomaterials, microscale technologies, gene editing technologies, and stem cell biology have enabled the construction of human specific brain structures in vitro. However, the limitations of long-term culture, necrosis, and hypoxic cores in different culture models obstruct brain organoid growth and survival. The in vitro models should facilitate oxygen and nutrient absorption, which is essential to generate complex organoids and provides a biomimetic microenvironment for modeling human brain organogenesis and human diseases. This review aims to highlight the progress in the culture devices of brain organoids, including dish, bioreactor, and organ-on-a-chip models. With the modulation of bioactive molecules and biomaterials, the generated organoids recapitulate the key features of the human brain in a more reproducible and hyperoxic fashion. Furthermore, an outlook for future preclinical studies and the genetic modifications of brain organoids is presented.
脑类器官是源自人诱导多能干细胞（hiPSC）的三维自组装结构。它们可以重现大脑的时空组织和功能，为体外脑发育、进化和疾病建模提供了强大的系统。生物材料、微尺度技术、基因编辑技术和干细胞生物学的重大进展使得在体外构建人类特异性脑结构成为可能。然而，不同培养模型中长期培养、坏死和缺氧核心的限制阻碍了脑类器官的生长和存活。体外模型应促进氧气和营养物质的吸收，这对于生成复杂的类器官至关重要，并为模拟人类大脑发生和人类疾病提供了仿生微环境。本文旨在强调脑类器官培养装置的研究进展，包括培养皿、生物反应器和器官芯片模型。通过对生物活性分子和生物材料的调控，生成的类器官以更可重复和高氧的方式重现人类大脑的关键特征。此外，还对未来的临床前研究和脑类器官的基因修饰进行了展望。
