2026-10-10T20:01:24Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34012932 2026-09-28T10:37:09Z category_7 portal_147 item_type_3 month_year_09_2026

Supplemental Material for: Endothelial-Fibroblast Organoids Generated in Hydrogel Microchamber Arrays: A Translational Model of Vascular Dysfunction in Cardio-Kidney-Metabolic Disease figshare admin karger (2628495) Tali Zitman-Gal (9702370) Maria Sobolev (1524571) Anna Talash (25121719) Shelly Tartakover-Matalon (25121725) Guy Topaz (6235928) Jacob Chen (3633811) David Pereg (6235934) Gloria Rashid (22555733) Naomi Nacasch (25121741) Arik Dahan (434016) Mordechai Deutsch (1524556) Keren Cohen-Hagai (25121748) Medicine Medicine <p dir="ltr"><a href="" target="_blank"><b>Introduction</b></a>: Cardio-kidney-metabolic (CKM) disease comprises interconnected cardiovascular, renal, and metabolic disorders in which endothelial dysfunction drives microvascular and macrovascular injury. Although novel treatments improve clinical outcomes, the cellular and molecular mechanisms underlying these effects remain incompletely understood. Addressing this gap requires experimental systems that recapitulate the structural and functional complexity of the vascular microenvironment. The objective of this study was to establish and characterize a three-dimensional (3D) endothelial and fibroblast co-culture platform for controlled investigation of endothelial morphogenesis, stromal interactions, and responses to metabolic and pharmacological stimuli.</p><p dir="ltr"><b>Methods:</b> We developed a hydrogel microchamber array (HMC) platform enabling reproducible formation of endothelial spheroids and extracellular matrix - embedded organoids. Human umbilical vein endothelial cells (HUVECs) were cultured alone or with NIH3T3 fibroblasts, allowing direct comparison of growth configurations within a defined 3D microenvironment. Morphometric parameters were quantified longitudinally following glucose exposure to model diabetic-like conditions and treatment with a glucagon-like peptide-1 receptor agonist/insulin combination (Xultophy)<b>.</b></p><p dir="ltr"><b>Results:</b> The HMC platform supported reproducible formation of monolayers, scaffold-free spheroids, and matrix-embedded organoids. Fibroblast co-culture enhanced endothelial organization and structural complexity. Glucose exposure induced time-dependent increases in organoid size and reduced circularity, indicating structural remodeling. Xultophy treatment moderated these effects and preserved higher circularity. Sequential stimulation revealed order-dependent responses, with Xultophy partially attenuating glucose-induced expansion. Organoids exhibited stronger responses than spheroids, underscoring the role of extracellular matrix context.</p><p dir="ltr"><b>Conclusion</b>: The HMC system provides a reproducible platform for studying endothelial morphogenesis and stromal regulation in physiologically relevant 3D environments, enabling controlled investigation of endothelial responses to metabolic stress and therapeutic modulation</p> 2026-09-28T10:37:09Z Dataset Dataset 10.6084/m9.figshare.34012932.v1 https://figshare.com/articles/dataset/Supplemental_Material_for_Endothelial-Fibroblast_Organoids_Generated_in_Hydrogel_Microchamber_Arrays_A_Translational_Model_of_Vascular_Dysfunction_in_Cardio-Kidney-Metabolic_Disease/34012932 CC BY 4.0