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application of organoid models in disease mechanism 2. Breakthrough strategies for organoid
analysis, drug screening, and regenerative medicine, whereas construction
excluding studies that primarily addressed basic technical
optimizations without substantial applied contributions. Recent advancements in organoid construction have gone
We emphasized articles from high-impact journals beyond traditional stem cell-derived models, exploring
that had been widely cited, particularly those featuring innovative approaches to develop organoids from various
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methodological innovations such as artificial intelligence tissue sources. This paradigm shift enables the creation
(AI) integration and organoid functionalization. Finally, of organoids that better capture the unique characteristics
only studies with robust experimental validation, including and functions of specific tissues, providing more accurate
single-cell RNA sequencing and comprehensive in vivo and models for studying development, disease mechanisms,
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in vitro assessments, were included to ensure the reliability and therapeutic responses. In addition, breakthroughs in
and credibility of the findings. material science have paved the way for precisely regulated
organoid development. By designing biomaterials
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One of the major advancements of 2024 was the that mimic the native extracellular matrix (ECM) and
development of brain organoids with anatomical region modulating mechanical and biochemical cues, researchers
specificity, which replicate distinct brain regions, such can guide organoid self-organization and maturation.
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as the cortex and hippocampus, with high fidelity. These These strategies represent a significant leap forward,
organoids provide an advanced platform for studying offering new possibilities for personalized medicine, tissue
neurodevelopmental disorders, such as autism and engineering, and regenerative therapies.
schizophrenia, offering novel insights into the genetic
and environmental factors affecting specific brain 2.1. Brain organoids with anatomical region specificity
regions. Similarly, the creation of amniotic fluid (AF)- Recent advancements in brain organoid technology have
based organoids revolutionized prenatal diagnostics by led to the development of organoids with anatomical region
enabling the modeling of fetal development and the non- specificity, a significant leap beyond traditional models
invasive detection of congenital diseases. In oncology, that are derived from pluripotent or adult stem cells.
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2024 saw the emergence of organoid models capable of Unlike conventional organoids, which generally provide a
identifying carcinogenic factors and simulating tumor generalized representation of the brain, these new models
progression with unprecedented precision. For instance, are generated directly from fetal brain tissue, enabling
engineered “mini-colons” demonstrated spatiotemporal the creation of organoids that exhibit the distinct cellular
tumorigenesis in vitro, facilitating the study of cancer composition and functional characteristics of specific brain
heterogeneity and the role of gut microbiota in tumor regions, such as the cortex, hippocampus, or basal ganglia.
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development. In addition, immune-competent organoids This innovation allows for a more accurate replication of the
integrated tissue-resident immune cells, allowing complex architecture and cellular organization seen in the
researchers to explore immune-mediated processes in human brain, making it a valuable tool for studying regional
gut inflammation, autoimmune diseases, and cancer brain development and pathology. Region-specific brain
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immunotherapy. The integration of AI with organoid organoids hold particular promise for investigating the
technology has marked another significant milestone. underlying mechanisms of neurodevelopmental disorders,
AI-assisted organoids enabled high-throughput drug including autism spectrum disorders, schizophrenia,
screening, improved the identification of therapeutic and intellectual disabilities, as they provide insights into
targets, and paved the way for precision medicine by how genetic and environmental factors affect different
tailoring treatments to individual genetic profiles. brain regions. Thus, brain organoids with anatomical
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Furthermore, advances in bioengineering, such as region specificity represent an important advancement in
the development of large-scale, self-mineralizing the field of neuroscience, offering new opportunities for
bone organoids and DNA microbead technologies for understanding brain function and disease.
spatiotemporal control, addressed critical limitations in During development, the human brain exhibits
scalability, vascularization, and tissue complexity.
a unique capacity for expansion while concurrently
This review highlights the latest advancements in establishing cellular differentiation, diversity, and
organoid technology, focusing on breakthrough strategies complex tissue architecture. 17,18 However, the successful
for organoid construction, enhanced disease modeling, translation of these intrinsic brain characteristics into
and transformative applications (Figure 1). By addressing long-term, expanding, 3D in vitro culture systems has
critical challenges and showcasing innovative approaches, not been achieved. Benedetta Artegiani and Hans Clevers
this work underscores the pivotal role of organoids in led their research team in the Netherlands to generate
reshaping the future of biomedical research and therapeutic long-term expanding central nervous system (CNS)
development. organoids from human fetal tissue. They demonstrated
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Volume 1 Issue 2 (2025) 2 doi: 10.36922/OR025040005