Dissecting endothelial cell heterogeneity with new toolsZhong, Gao, Zhang
et alCell Regen (2025) 14 (1), 10
Abstract: The formation of a blood vessel network is crucial for organ development and regeneration. Over the past three decades, the central molecular mechanisms governing blood vessel growth have been extensively studied. Recent evidence indicates that vascular endothelial cells-the specialized cells lining the inner surface of blood vessels-exhibit significant heterogeneity to meet the specific needs of different organs. This review focuses on the current understanding of endothelial cell heterogeneity, which includes both intra-organ and inter-organ heterogeneity. Intra-organ heterogeneity encompasses arterio-venous and tip-stalk endothelial cell specialization, while inter-organ heterogeneity refers to organ-specific transcriptomic profiles and functions. Advances in single-cell RNA sequencing (scRNA-seq) have enabled the identification of new endothelial subpopulations and the comparison of gene expression patterns across different subsets of endothelial cells. Integrating scRNA-seq with other high-throughput sequencing technologies promises to deepen our understanding of endothelial cell heterogeneity at the epigenetic level and in a spatially resolved context. To further explore human endothelial cell heterogeneity, vascular organoids offer powerful tools for studying gene function in three-dimensional culture systems and for investigating endothelial-tissue interactions using human cells. Developing organ-specific vascular organoids presents unique opportunities to unravel inter-organ endothelial cell heterogeneity and its implications for human disease. Emerging technologies, such as scRNA-seq and vascular organoids, are poised to transform our understanding of endothelial cell heterogeneity and pave the way for innovative therapeutic strategies to address human vascular diseases.© 2025. The Author(s).
Establishment and validation of red fox (vulpes vulpes) airway epithelial cell cultures at the air-liquid-interfaceOehm, Esteves, Hetzel
et alSci Rep (2025) 15 (1), 9883
Abstract: The airway epithelium represents a central barrier against pathogens and toxins while playing a crucial role in modulating the immune response within the upper respiratory tract. Understanding these mechanisms is particularly relevant for red foxes (Vulpes vulpes), which serve as reservoirs for various zoonotic pathogens like rabies or the fox tapeworm (Echinococcus multilocularis). The study aimed to develop, establish, and validate an air-liquid interface (ALI) organoid model of the fox respiratory tract using primary airway epithelial cells isolated from the tracheas and main bronchi of hunted red foxes. The resulting ALI cultures exhibited a structurally differentiated, pseudostratified epithelium, characterised by ciliated cells, mucus secretion, and tight junctions, as confirmed through histological and immunohistochemical analysis. Functional assessments using a paracellular permeability assay and measurement of transepithelial electrical resistance, demonstrated a tight epithelial barrier. The potential of model's utility for studying innate immune responses to respiratory infections was validated by exposing the cultures to lipopolysaccharide, phorbol-12-myristate-13-acetate and ionomycin, and nematode somatic antigens. Quantitative PCR revealed notable changes in the expression of pro-inflammatory cytokines TNF and IL-33. This in vitro model represents a significant advancement in respiratory research for non-classical species that may act as important wildlife reservoirs for a range of zoonotic pathogens.© 2025. The Author(s).
Treatment Adherence to Adjuvant Chemotherapy According to the New Standard 3-month CAPOX Regimen in High-risk Stage II and Stage III Colon Cancer: A Population-based Evaluation in The Netherlandsvan den Berg, van Erning, Burger
et alClin Colorectal Cancer (2025)
Abstract: A 3-month adjuvant treatment regimen with capecitabine and oxaliplatin (CAPOX) for high-risk stage II (T4N0) and stage III (node-positive) colon cancer was implemented in the Netherlands in 2017. The IDEA trial showed a clinically irrelevant difference in long-term outcomes in combination with a substantial decrease in toxicity in comparison with a 6-month regimen. A significantly increased dose intensity was observed in the 3-month arm, which might be essential to achieve optimal long-term outcomes. Hence, the aim of the present study was to evaluate if a similar dose intensity could be achieved in patients treated with adjuvant CAPOX for 3 months in daily practice.Patients scheduled for 3 months of adjuvant CAPOX for high-risk stage II or stage III colon cancer were selected from the Netherlands Cancer Registry. The number of administered cycles and the daily cumulative dose of capecitabine and oxaliplatin were extracted from the medical files. Relative dose intensity (RDI) was determined by comparing the administered dose intensity with the standard dose intensity.In total, 802 (80.0%) of the 1002 patients completed 4 cycles of CAPOX. The overall mean RDI of adjuvant treatment was 82.9% for capecitabine, and 83.8% for oxaliplatin, based on the combination of dose reductions and omitting cycles.One out of 5 patients did not complete 4 cycles of CAPOX. The administered dose of capecitabine and oxaliplatin in the first year after the update of the guideline was lower than the advised dose for the 3-month CAPOX regimen, and the administered dose in the IDEA study. The impact on long-term oncological outcomes should be awaited.Copyright © 2025. Published by Elsevier Inc.
Correction of the Allan-Herndon-Dudley syndrome-causing SLC16A2 mutation G401R in a patient derived hiPSC lineLudwik, Opitz, Jyrch
et alStem Cell Res (2025) 85, 103698
Abstract: The X-linked Allan-Herndon-Dudley syndrome (AHDS) is a genetic disorder characterized by severe psychomotor impairment, resulting from mutations in the SLC16A2 gene, which encodes the thyroid hormone transporter MCT8 (monocarboxylate transporter 8). Previously, we established a hiPSC line from a patient carrying the SLC16A2:R401G mutation (BIHi045-A). Using CRISPR/Cas9-mediated gene editing, we targeted exon 3 of SLC16A2 and used single-stranded oligodeoxynucleotides as homology-directed repair templates to correct the R401G missense mutation, generating an isogenic control cell line.Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
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