Evolving from organoid to assembloid with enhanced cellular interactions

Abstract

In Brief This review explores the emerging field of assembloid technology, which integrates multiple organoids or cell types into self-organizing three-dimensional (3D) systems to better model inter-tissue communication. It categorizes assembloids into four key assembly strategies and discusses their applications across various human systems, while also addressing challenges and future prospects. Graphical abstract Highlights ■ Detailed analysis of the four key assembly strategies for building physiologically relevant assembloids: multi-region, multi-lineage, multi-gradient, and multi-layer. ■ Application of assembloids in modeling complex interactions across human systems, including the nervous, digestive, urinary, reproductive, and circulatory systems. ■ Identification of key challenges such as reproducibility and vascularization, with proposed solutions using bioengineering techniques and artificial intelligence to improve model accuracy and functionality. ABSTRACT In recent years, the study of complex cellular interactions has been hampered by the limitations of traditional two-dimensional (2D) and single-cell type culture systems, which fail to accurately mimic the intricate dynamics of human tissues. To bridge this gap, assembloid technology has emerged as a transformative approach. Assembloids are self-organizing three-dimensional (3D) systems formed by integrating multiple organoids or cell types, providing a more accurate model for studying inter-tissue and inter-organ communication. Here, we categorize current assembloids into four types based on assembly strategies-multi-region, multi-lineage, multi-gradient, and multi-layer-each designed to replicate specific biological phenomena with high fidelity. We also explore the diverse applications of assembloids across various human systems, demonstrating the broad application scope of assembloids. Finally, we highlight the challenges faced by assembloid technology and outline its future prospects. Overall, assembloids represent a powerful platform for advancing research in developmental biology, disease modeling, and drug discovery.