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Abstract
Current 2D and 3D models of the kidney glomerulus are imperfect for drug screening. This paper introduces GlomSpheres, a rapidly generated and reproducible 3D co-culture spheroid model. Using magnetic spheroid formation, human podocytes and glomerular endothelial cells (GEnCs) form organized collagen IV and laminin. Key podocyte and GEnC markers are upregulated, and electron microscopy shows foot process interdigitation and vessel formation. Treatment with profibrotic agents induces ECM dysregulation and podocyte loss, attenuated by Nintedanib. Incubation with patient plasma shows podocyte loss and ECM dysregulation, also reduced by Nintedanib. A rapid imaging approach demonstrates GlomSpheres' utility in high-throughput pharmaceutical screening.
Publisher
Communications Biology
Published On
Dec 02, 2021
Authors
Jack Tuffin, Musleeha Chesor, Valeryia Kuzmuk, Tim Johnson, Simon C. Satchell, Gavin I. Welsh, Moin A. Saleem
Tags
GlomSpheres
3D model
kidney glomerulus
drug screening
podocytes
glomerular endothelial cells
Nintedanib

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