[Current progress in brain organoid research for human biology].
TL;DR
The development of brain organoid research is reviewed and recent advances including neuronal activity measurements, neural circuit models using assembloids and connectoids, reconstruction of human-enriched cell types and gene programs, analyses of inter-individual variability, toxicological studies, disease modeling, and drug evaluation are discussed.
Abstract
Understanding human brain development, function, disease, and drug responses remains a central challenge in neuroscience and medicine. However, detailed analyses of living human brain tissue are technically and ethically difficult, and conventional studies have therefore relied largely on animal models and two-dimensional culture systems. Nevertheless, substantial differences exist between humans and animals in developmental processes, cellular composition, neural circuit, and pharmacological responses. Brain organoids are three-dimensional neural tissues generated from human embryonic stem cells or induced pluripotent stem cells, and they can recapitulate aspects of neural progenitor differentiation, cellular diversity, tissue architecture, and neuronal activity. Owing to these properties, brain organoids provide a valuable platform for human biology research. In this article, we review the development of brain organoid research and discuss recent advances including neuronal activity measurements, neural circuit models using assembloids and connectoids, reconstruction of human-enriched cell types and gene programs, analyses of inter-individual variability, toxicological studies, disease modeling, and drug evaluation. Furthermore, we outline the current status and future perspectives of human biology research using brain organoids, with particular attention to challenges such as heterogeneity, limited maturation, the absence of vascular and immune systems, standardization, quality control, and ethical considerations.