From liver organoids to regulatory platforms for precision hepatology: Advances and challenges

Liver Organoids: From Disease Modelling to Regenerative Medicine

This review systematically summarises current fabrication strategies, disease‐modelling utilities and regenerative potentials of liver organoids, alongside the major challenges and future directions.

Leveraging IGF signaling to improve the spatial organization and regenerative potential of iPSC-derived vascularized liver organoids

Vascularized liver organoids are developed by integrating human induced pluripotent stem cell (iPSC)–derived hepatoblasts and endothelial cells into decellularized scaffolds functionalized with an anti-CD31 aptamer–based vascular coating agent (VCA) to establish a comprehensive framework for generating physiologically relevant liver tissues from iPSCs and demonstrate the utility of spatial transcriptomics for uncovering regenerative mechanisms.

Function-First Organoid Engineering for Regenerative Medicine: Current Challenges and Future Perspectives.

A function-first framework in which regenerative organoids are engineered and evaluated according to measurable therapeutic outcomes, including tissue-specific function, vascular integration, immune compatibility, reproducibility, scalability, and long-term stability is proposed.

Emerging Role of Human Organoids in Drug Discovery and Development: Current Advances and Challenges

Engineering Neural Organoids: Technological Advances and Translational Frontiers.

Neural organoids have transformed experimental neuroscience by enabling human-specific models of brain development, function, and disease. Emerging at the intersection of stem cell biology and tissue engineering, these self-organizing systems recapitulate key aspects of neurogenesis, gliogenesis, and circuit formation within a controllable in vitro context. Advances in guided patterning, vascularization, and electrophysiological monitoring have enhanced structural and functional fidelity, enabling the study of dynamic processes previously inaccessible in human models. Beyond developmental biology, neural organoids have broad translational applications, including modeling neurodevelopmental and neurodegenerative disorders, screening pharmacological compounds, and testing regenerative strategies. Integration with microfluidics, bioelectronic interfaces, and computational modeling further expands their analytical capacity, transforming organoids into modular and quantifiable platforms for mechanistic and therapeutic discovery. Despite this progress, key challenges remain, including limited maturation, inter-organoid variability, and incomplete physiological integration. Addressing these limitations requires standardized differentiation protocols, robust functional benchmarks, and cross-disciplinary collaboration. The goal is not to replicate the brain in miniature, but to reconstruct its organizing principles in an experimentally accessible system. From this perspective, neural organoids serve as a bridge between biology and technology, offering new insights into human neural complexity while advancing neuroscience and medicine.

The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances

Highlights What are the main findings? Primary hepatocytes are notoriously difficult to maintain long-term in vitro, but defined growth-factor protocols can reversibly convert them into a proliferative, progenitor-like state before restoring maturity. Three-dimensional (3D) culture strategies improve hepatocyte maturation but remains limited in scalability. What are the implication of the main finding? Integrating reprogramming, pathway modulation, and 3D-culture strategies is recommended to build a functionally stable hepatocyte platform. The translation of findings from animal studies to humans should be carefully considered before clinical application. Abstract The adult liver exhibits remarkable regenerative capacity in vivo; however, primary hepatocytes (PHs), the principal functional cells of the liver, swiftly forfeit their proliferative potential and specialized hepatic functions when isolated from their native microenvironment and cultured in vitro. While PHs are the benchmark for studying hepatic physiology, xenobiotic metabolism, and toxicological responses, their rapid dedifferentiation resulting in the loss of hepatic functions significantly limits their further application. Recent studies suggest three converging strategies to address the challenge of long-term maintenance and expansion of PHs. First, defined chemical and growth factor-based protocols can temporarily induce hepatocytes into a proliferative, progenitor-like state, followed by a maturation phase that restores differentiated hepatic functions. In addition, the inhibition of signaling pathways linked to cellular stress responses and identity loss can postpone dedifferentiation and preserve drug-metabolizing activity for prolonged durations, thereby enhancing disease modeling and toxicology studies. Finally, three-dimensional (3D) culture platforms generally improve hepatocyte maturation and functional stability, but these are often not scalable due to matrix dependence, technical complexity, handling requirements, and cost. This review thoroughly examines innovative methodological advancements designed to facilitate the proliferation and prolonged viability of healthy PHs, focusing on their translational relevance and clinical applicability.