Uteroplacental microvascular remodeling in health and diseaseLi, Ma, Geng
et alActa Physiol (Oxf) (2025) 241 (5), e70035
Abstract: The microvascular system is essential for delivering oxygen and nutrients to tissues while removing metabolic waste. During pregnancy, the uteroplacental microvascular system undergoes extensive remodeling to meet the increased demands of the fetus. Key adaptations include vessel dilation and increases in vascular volume, density, and permeability, all of which ensure adequate placental perfusion while maintaining stable maternal blood pressure. Structural and functional abnormalities in the uteroplacental microvasculature are associated with various gestational complications, posing both immediate and long-term risks to the health of both mother and infant. In this review, we describe the changes in uteroplacental microvessels during pregnancy, discuss the pathogenic mechanisms underlying diseases such as preeclampsia, fetal growth restriction, and gestational diabetes, and summarize current clinical and research approaches for monitoring microvascular health. We also provide an update on research models for gestational microvascular complications and explore solutions to several unresolved challenges. With advancements in research techniques, we anticipate significant progress in understanding and managing these diseases, ultimately leading to new therapeutic strategies to improve maternal and fetal health.© 2025 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
Advances in humanoid organoid-based research on inter-organ communications during cardiac organogenesis and cardiovascular diseasesNi, Ye, Zhang
et alJ Transl Med (2025) 23 (1), 380
Abstract: The intimate correlation between cardiovascular diseases and other organ pathologies, such as metabolic and kidney diseases, underscores the intricate interactions among these organs. Understanding inter-organ communications is crucial for developing more precise drugs and effective treatments for systemic diseases. While animal models have traditionally been pivotal in studying these interactions, human-induced pluripotent stem cells (hiPSCs) offer distinct advantages when constructing in vitro models. Beyond the conventional two-dimensional co-culture model, hiPSC-derived humanoid organoids have emerged as a substantial advancement, capable of replicating essential structural and functional attributes of internal organs in vitro. This breakthrough has spurred the development of multilineage organoids, assembloids, and organoids-on-a-chip technologies, which allow for enhanced physiological relevance. These technologies have shown great potential for mimicking coordinated organogenesis, exploring disease pathogenesis, and facilitating drug discovery. As the central organ of the cardiovascular system, the heart serves as the focal point of an extensively studied network of interactions. This review focuses on the advancements and challenges of hiPSC-derived humanoid organoids in studying interactions between the heart and other organs, presenting a comprehensive exploration of this cutting-edge approach in systemic disease research.© 2025. The Author(s).
Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicityShaker, Salloum-Asfar, Taha
et alMol Brain (2025) 18 (1), 27
Abstract: Klotho, a well-known aging suppressor protein, has been implicated in neuroprotection and the regulation of neuronal senescence. While previous studies have demonstrated its anti-aging properties in human brain organoids, its potential to mitigate neurodegenerative processes triggered by β-amyloid remains underexplored. In this study, we utilised human induced pluripotent stem cells (iPSCs) engineered with a doxycycline-inducible system to overexpress KLOTHO and generated 2D cortical neuron cultures from these cells. These neurons were next exposed to pre-aggregated β-amyloid 1-42 oligomers to model the neurotoxicity associated with Alzheimer's disease. Our data reveal that upregulation of KLOTHO significantly reduced β-amyloid-induced neuronal degeneration and apoptosis, as evidenced by decreased cleaved caspase-3 expression and preservation of axonal integrity. Additionally, KLOTHO overexpression prevented the loss of dendritic branching and mitigated reductions in axonal diameter, hallmark features of neurodegenerative pathology. These results highlight Klotho's protective role against β-amyloid-induced neurotoxicity in human cortical neurons and suggest that its age-related decline may contribute to neurodegenerative diseases such as Alzheimer's disease. Our findings underscore the therapeutic potential of Klotho-based interventions in mitigating age-associated neurodegenerative processes.© 2025. The Author(s).
Hepatotoxicity evaluation method through multiple-factor analysis using human pluripotent stem cell derived hepatic organoidsShin, Yang, Jeong
et alSci Rep (2025) 15 (1), 10804
Abstract: Prediction of the potential for drug-induced liver injury (DILI) in the early stages of drug development is important. We developed an organoid-based and functional endpoint method for accurate prediction of DILI. To this end, hepatic organoids (HOs) derived from human pluripotent stem cells (hPSCs) were cocultured with hepatic stellate cells (HSCs) and THP-1 macrophages in Matrigel domes to mimic the cellular and physiological environment of the human liver. To validate our hepatotoxicity prediction model, we selected 12 hepatotoxic reference compounds. As indicators, we used factors related to mechanisms of hepatotoxicity and markers thereof, including factors related to oxidative stress and proinflammatory cytokines. We plotted radar graphs and calculated the relative areas of polygons to analyze the effects of drugs with different degrees of hepatotoxicity. The drugs in the severe DILI group significantly increased the levels of factors related to oxidative stress (ROS, GSSH, and catalase) compared to those in the no and mild DILI groups. The drugs in the severe group significantly increased the levels of inflammation-related factors (IL-1, IL-6, and IL-10). The drugs in the mild and severe groups highly significantly increased the activities of ALT and AST and the level of ALB compared to those in the no DILI group. In summary, the drugs in the severe DILI group had significantly greater effects on the factors analyzed than those in the no DILI group. Therefore, our hepatotoxicity evaluation method is suitable for predicting DILI in the early stages of drug development.© 2025. The Author(s).
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