Jul 2026· Current Opinion in Genetics and Development· Vol 100, pp.
102512
· 1 citation· 53 references
Medicine
TL;DR
This review discusses how organoids and OoC-based platforms are being leveraged to study and enhance cell fate reprogramming, repair, and regeneration across multiple tissues and outlines current limitations, including scalability, standardization, and biomaterial constraints.
Abstract
Recent advances in genetic engineering and in vivo reprogramming have opened transformative possibilities for controlling cell fate in tissue repair and regeneration. However, clinical translation remains constrained by the limited predictive value of animal models and traditional in vitro systems, which often fail to fully recapitulate human responses, including the physiological consequences of genetic manipulations. Emerging microphysiological systems, exemplified by three-dimensional organoids and organs-on-chips (OoCs) systems, help bridge this gap by recreating key aspects of human physiology while enabling precise bioengineering of the niche to modulate cell fate decisions and plasticity. Organoids derived from induced pluripotent stem cells, adult stem cells, primary tissues, or directly reprogrammed cells preserve the patient-specific genetic background, facilitating mechanistic studies of development and disease and the evaluation of gene correction and reprogramming strategies in a human-relevant context. Complementarily, OoC platforms provide regulated perfusion, tissue vascularization, mechanical forces, molecular gradients, and immune cell integration to promote tissue maturation, functional readouts, and quantitative assessment of therapeutic responses that are difficult to achieve in static cultures. In this review, we discuss how organoids and OoC-based platforms are being leveraged to study and enhance cell fate reprogramming, repair, and regeneration across multiple tissues. We highlight recent reports where these systems informed the design, optimization, and safety evaluation of gene and cell therapies. Finally, we outline current limitations, including scalability, standardization, and biomaterial constraints, and propose future directions for integrating organoids, OoC, and gene-modulation technologies to enable more predictive, personalized, and clinically translatable regenerative medicine.
Recognising the central role of VSELs/progenitors and their niche in maintaining tissue homeostasis in vivo could resolve existing roadblocks and guide more effective endogenous regenerative therapies for diseased tissues and age-related dysfunctions.
D. Bhartiya, N. Sharma, Anish Tripathi et al.· Stem Cell Reviews and Report...· 0 citations
This review summarizes the trajectory of iPSC reprogramming technologies and identifies the core “translational triltrilas”, namely, the inherent tradeoffs between security, homogeneity, and scalability, and proposes a comprehensive strategy to overcome these bottlenecks.
Mengmeng Chen, Ning Zuo, Qi Wang et al.· Frontiers in Cell and Develo...· 0 citations
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.
Sungmin Kim, H. Jo, Sunghwan Moon· Stem Cells· 0 citations
Key applications of iPSC technology in hemato-oncology are summarized, its major advantages and current limitations are discussed, and emerging directions are highlighted, including scalable iPSC-derived blood cell therapies for inherited and acquired bone marrow failure syndromes and leukemia.
Ivan Tesakov, M. Nasri, M. Klimiankou et al.· Frontiers in Immunology· 0 citations
Evidence that cell-type-specific promoters lose fidelity when paired with neurogenic transgene payloads and that published in vivo reprogramming efficiencies may be substantially confounded by promoter leakage in the absence of formal lineage tracing are synthesized.
Mariam Abdelnaby, A. Galiakberova, E. Dashinimaev· International Journal of Mol...· 0 citations
Human vascular function depends on tightly coordinated structural, mechanical, and cellular interactions, yet these features remain difficult to recapitulate in vitro. Induced pluripotent stem cells (iPSCs) enable efficient generation of vascular cell types, including endothelial cells, smooth muscle cells, and pericytes, but current systems often lack functional maturity and physiological relevance. Recent advances in vascular organoid engineering provide new opportunities to address this limitation. By integrating self-organization, co-culture, and bioengineering approaches, iPSC-derived systems can form three-dimensional vascular networks with increasing physiological relevance. Emerging evidence from studies of iPSC-derived vascular systems, spanning both two-dimensional differentiation models and three-dimensional organoid platforms, highlights the critical roles of hemodynamic cues, including shear stress and perfusion, together with metabolic and immune signaling, in driving the coordinated maturation of endothelial and mural compartments. These platforms enable modeling of key vascular pathologies, including inflammation, vascular remodeling, and barrier dysfunction, while gene editing further facilitates mechanistic investigation in patient-specific contexts. Together, iPSC-derived vascular systems provide a scalable and physiologically relevant platform for disease modeling, drug discovery, and regenerative medicine.
Chonggui Jiang, Pan Cui, Liyan Gong· Vascular pharmacology· 0 citations