人脑组织器官的应用——在模拟人脑发育和神经发育性疾病中的机遇与挑战。
Application of Human Brain Organoids-Opportunities and Challenges in Modeling Human Brain Development and Neurodevelopmental Diseases.
发表日期:2023 Aug 07
作者:
Soo-Hyun Kim, Mi-Yoon Chang
来源:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
摘要:
大脑器官样体是由人类多能干细胞(hPSCs)衍生的三维结构,其反映了早期的脑组织结构。这些器官样体包含多种细胞类型,包括神经元和胶质细胞,与人脑中的细胞类型相似。人脑器官样体为研究在动物模型中不太能体现的人脑发育特征提供了独特机会。与传统细胞培养和动物模型相比,脑器官样体更准确地代表了人脑的发育和功能,使其成为研究神经发育性疾病的合适模型。特别是来自患者细胞的脑器官样体已经使研究人员能够研究不同阶段的疾病,并更好地理解疾病机制。多脑区装配体允许研究不同脑区之间的相互作用,同时在分子和功能特异性上实现更高的一致性。尽管器官样体具有潜在的优点,但其实用性受到一些未解决的限制的限制,包括细胞压力、缺氧、坏死、缺乏高保真细胞类型、有限的成熟和电路形态等。在本综述中,我们将讨论克服脑器官样体的自然限制的研究,强调包括胶质细胞(星形胶质细胞、髓鞘细胞和微胶质细胞)和血管细胞在内的所有神经细胞类型的组合的重要性。此外,考虑到器官样体与发育中的大脑的相似性,地区模式的脑器官样体衍生的神经干细胞(NSCs)可作为可扩展的细胞替代治疗来源。我们重点介绍了脑器官样体衍生细胞在疾病细胞治疗中的潜在应用。
Brain organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that reflect early brain organization. These organoids contain different cell types, including neurons and glia, similar to those found in the human brain. Human brain organoids provide unique opportunities to model features of human brain development that are not well-reflected in animal models. Compared with traditional cell cultures and animal models, brain organoids offer a more accurate representation of human brain development and function, rendering them suitable models for neurodevelopmental diseases. In particular, brain organoids derived from patients' cells have enabled researchers to study diseases at different stages and gain a better understanding of disease mechanisms. Multi-brain regional assembloids allow for the investigation of interactions between distinct brain regions while achieving a higher level of consistency in molecular and functional characterization. Although organoids possess promising features, their usefulness is limited by several unresolved constraints, including cellular stress, hypoxia, necrosis, a lack of high-fidelity cell types, limited maturation, and circuit formation. In this review, we discuss studies to overcome the natural limitations of brain organoids, emphasizing the importance of combinations of all neural cell types, such as glia (astrocyte, oligodendrocytes, and microglia) and vascular cells. Additionally, considering the similarity of organoids to the developing brain, regionally patterned brain organoid-derived neural stem cells (NSCs) could serve as a scalable source for cell replacement therapy. We highlight the potential application of brain organoid-derived cells in disease cell therapy within this field.