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The following is a summary of “From morphology to single-cell molecules: high-resolution 3D histology in biomedicine,” published in the March 2025 issue of Molecular Cancer by Xu et al.

High-resolution three-dimensional (3D) tissue analysis has revolutionized biomedical research by providing unprecedented insights into the spatial organization and molecular composition of biological tissues. This review traces the historical evolution of high-resolution 3D histology, emphasizing key technological advancements that have shaped the field and enabled the development of state-of-the-art imaging and analytical methodologies. Researchers categorize the principal families of high-resolution 3D histology techniques, including advanced microscopy-based imaging, tomographic approaches, single-cell and spatial omics technologies, computational modeling, and 3D tissue reconstruction methods such as organoids, spheroids, and bioprinted structures. 

A comprehensive evaluation of these techniques is provided, detailing their fundamental principles, capabilities, and inherent limitations. Furthermore, the study group highlights the diverse applications of single-cell and spatial 3D histology across various disciplines, including oncology, cardiology, neuroscience, immunology, developmental biology, and regenerative medicine. These approaches are proving invaluable for deciphering complex tissue architectures, uncovering cellular interactions within the tumor microenvironment, understanding neurodegenerative diseases at a subcellular level, and advancing precision medicine through improved disease modeling. Despite the significant strides made in recent years, several challenges persist in the widespread adoption and standardization of high-resolution 3D histology. Key obstacles include high technological and financial barriers to entry, inconsistencies in data reproducibility, ambiguous best practices for experimental design, and a lack of uniformity in methodological approaches. 

Addressing these challenges requires interdisciplinary collaboration, the establishment of standardized protocols, and the integration of artificial intelligence and computational tools to enhance data interpretation and cross-study comparability. This review provides a critical analysis of the current state of the field, identifies existing limitations, and proposes strategic recommendations to facilitate broader adoption and continued innovation in cellular 3D tissue analysis. Through these advancements, high-resolution 3D histology holds the potential to significantly impact both basic research and clinical practice, paving the way for improved diagnostics, therapeutic development, and personalized medicine.

Source: molecular-cancer.biomedcentral.com/articles/10.1186/s12943-025-02240-x