Organoids, Volume 4, Issue 2 (June 2025) – 4 articles

Basic and translational cancer biology research requires model systems that recapitulate the features of human tumors. While two-dimensional (2D) cell cultures have been foundational and allowed critical advances, they lack the organizational complexity, cellular interactions, and extracellular matrix present in vivo. Mouse models have thus remained the gold standard for studying cancer. In addition to high cost and low throughput, mouse models can also suffer from reduced tumor heterogeneity and species-specific differences. Three-dimensional (3D) culture models have emerged as a key intermediary between 2D cell lines and mouse models, with lower cost and greater flexibility than mouse models and a more accurate representation of the tumor microenvironment than 2D cell lines. In neuroblastoma, an aggressive childhood cancer, 3D models have been applied to study drug responses, cell motility, and tumor–matrix interactions. Recent advances include the integration of immune cells for immunotherapy studies, mesenchymal stromal cells for tumor–stroma interactions, and bioprinted systems to manipulate matrix properties. This review examines the use of 3D culture systems in neuroblastoma, highlighting their advantages and limitations while emphasizing their potential to bridge gaps between in vitro, preclinical, and clinical applications. By improving our understanding of neuroblastoma biology, 3D models hold promise for advancing therapeutic strategies and outcomes in this childhood cancer. Full article

The development of brain organoids from human-induced pluripotent stem cells (iPSCs) has expanded research into neurodevelopment, disease modeling, and drug testing. More recently, the concept of organoid intelligence (OI) has emerged, proposing that these constructs could evolve to support learning, memory, or even sentience. While this perspective has driven enthusiasm in the field of organoid research and suggested new applications in fields such as neuromorphic computing, it also introduces significant scientific and conceptual concerns. Current brain organoids lack the anatomical complexity, network organization, and sensorimotor integration necessary for intelligence or sentience. Despite this, claims surrounding OI often rely on oversimplified interpretations of neural activity, fueled by neurorealist and reification biases that misattribute neurophysiological properties to biologically limited systems. Beyond scientific limitations, the framing of OI risks imposing ethical and regulatory challenges based on speculative concerns rather than empirical evidence. The assumption that organoids might possess sentience, or could develop it over time, could lead to unnecessary restrictions on legitimate research while misrepresenting their actual capabilities. Additionally, comparing biological systems to silicon-based computing overlooks fundamental differences in scalability, efficiency, and predictability, raising questions about whether organoids can meaningfully contribute to computational advancements. The field must recognize the limitations of these models rather than prematurely defining OI as a distinct research domain. A more cautious, evidence-driven approach is necessary to ensure that brain organoids remain valuable tools for neuroscience without overstating their potential. To maintain scientific credibility and public trust, it is essential to separate speculative narratives from grounded research, thus allowing for continued progress in organoid studies without reinforcing misconceptions about intelligence or sentience. Full article

Recent research works have shown the effect of nutrient concentration on cell activity, such as proliferation and differentiation. In 3D cell culture, the impact of scaffold geometry, including pore size, strut diameter, and pore shape, on the concentration gradient within scaffolds under two different loading conditions—constant fluid perfusion and non-fluid perfusion—in a perfusion bioreactor is investigated by developing an in silico model of scaffolds. In this study, both triply periodic minimal surface (TPMS) (with gyroid struts) and non-TPMS (with cubic and spherical pores) scaffolds were investigated. Two types of criteria are applied to the scaffolds: static and perfusion culture conditions. In a static environment, the scaffold in a perfusion bioreactor is loaded with a fluid velocity of $0 \mathrm{m}\mathrm{m}/\mathrm{s}$, whereas in a dynamic environment, perfusion flow with a velocity of 1 mm/s is applied. The results of in silico simulation indicate that the concentration gradient within the scaffold is significantly influenced by pore size, strut diameter, pore shape, and fluid flow, which in turn affects the diffusion rate during drug delivery. Full article

Lymphoid organs are critical for organizing the development of the immune system, generating immune tolerance, and orchestrating the adaptive immune response to foreign antigens. Defects in their structure and function can lead to immunodeficiency, hypersensitivity, cancer, or autoimmune diseases. To better understand these diseases and assess potential therapies, complex models that recapitulate the anatomy and physiology of these tissues are required. Organoid models possess a number of advantages, including complex 3D microarchitecture, scalability, and personalization, which make them ideal for modelling lymphoid organs and related pathologies. Organoids have been developed for both primary and secondary lymphoid tissues; however, these models possess several limitations, including immature phenotypes and incomplete stromal cell populations. Furthermore, these organoids are often heterogeneous in both structure and function. Several lymphoid organs, such as the spleen, do not yet have robust organoid models, offering opportunities for breakthroughs in the field. Overall, development of lymphoid organoids will pave the way for the rapid development and testing of novel therapies, organ modelling, and personalized medicine. This review summarizes current advances in models for the primary lymphoid organ—bone marrow and thymus—as well as the secondary lymphoid organs of the lymph node and spleen. Full article