Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk
The glomerulus is a compact cluster of capillaries responsible for blood filtration and initiating urine production in the renal nephrons. A trilaminar structure in the capillary wall forms the glomerular filtration barrier (GFB), composed of glycocalyx-enriched and fenestrated endothelial cells adh...
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doaj-70285113b56c444094ecb23d8c80ba432021-06-02T06:53:31ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-06-011210.3389/fphys.2021.689083689083Modeling the Glomerular Filtration Barrier and Intercellular CrosstalkKerstin Ebefors0Emelie Lassén1Nanditha Anandakrishnan2Evren U. Azeloglu3Ilse S. Daehn4Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesThe glomerulus is a compact cluster of capillaries responsible for blood filtration and initiating urine production in the renal nephrons. A trilaminar structure in the capillary wall forms the glomerular filtration barrier (GFB), composed of glycocalyx-enriched and fenestrated endothelial cells adhering to the glomerular basement membrane and specialized visceral epithelial cells, podocytes, forming the outermost layer with a molecular slit diaphragm between their interdigitating foot processes. The unique dynamic and selective nature of blood filtration to produce urine requires the functionality of each of the GFB components, and hence, mimicking the glomerular filter in vitro has been challenging, though critical for various research applications and drug screening. Research efforts in the past few years have transformed our understanding of the structure and multifaceted roles of the cells and their intricate crosstalk in development and disease pathogenesis. In this review, we present a new wave of technologies that include glomerulus-on-a-chip, three-dimensional microfluidic models, and organoids all promising to improve our understanding of glomerular biology and to enable the development of GFB-targeted therapies. Here, we also outline the challenges and the opportunities of these emerging biomimetic systems that aim to recapitulate the complex glomerular filter, and the evolving perspectives on the sophisticated repertoire of cellular signaling that comprise the glomerular milieu.https://www.frontiersin.org/articles/10.3389/fphys.2021.689083/fullglomerular filtration barriercrosstalkin vitropodocyteglomerular endothelial cell3D model |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kerstin Ebefors Emelie Lassén Nanditha Anandakrishnan Evren U. Azeloglu Ilse S. Daehn |
spellingShingle |
Kerstin Ebefors Emelie Lassén Nanditha Anandakrishnan Evren U. Azeloglu Ilse S. Daehn Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk Frontiers in Physiology glomerular filtration barrier crosstalk in vitro podocyte glomerular endothelial cell 3D model |
author_facet |
Kerstin Ebefors Emelie Lassén Nanditha Anandakrishnan Evren U. Azeloglu Ilse S. Daehn |
author_sort |
Kerstin Ebefors |
title |
Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk |
title_short |
Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk |
title_full |
Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk |
title_fullStr |
Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk |
title_full_unstemmed |
Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk |
title_sort |
modeling the glomerular filtration barrier and intercellular crosstalk |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2021-06-01 |
description |
The glomerulus is a compact cluster of capillaries responsible for blood filtration and initiating urine production in the renal nephrons. A trilaminar structure in the capillary wall forms the glomerular filtration barrier (GFB), composed of glycocalyx-enriched and fenestrated endothelial cells adhering to the glomerular basement membrane and specialized visceral epithelial cells, podocytes, forming the outermost layer with a molecular slit diaphragm between their interdigitating foot processes. The unique dynamic and selective nature of blood filtration to produce urine requires the functionality of each of the GFB components, and hence, mimicking the glomerular filter in vitro has been challenging, though critical for various research applications and drug screening. Research efforts in the past few years have transformed our understanding of the structure and multifaceted roles of the cells and their intricate crosstalk in development and disease pathogenesis. In this review, we present a new wave of technologies that include glomerulus-on-a-chip, three-dimensional microfluidic models, and organoids all promising to improve our understanding of glomerular biology and to enable the development of GFB-targeted therapies. Here, we also outline the challenges and the opportunities of these emerging biomimetic systems that aim to recapitulate the complex glomerular filter, and the evolving perspectives on the sophisticated repertoire of cellular signaling that comprise the glomerular milieu. |
topic |
glomerular filtration barrier crosstalk in vitro podocyte glomerular endothelial cell 3D model |
url |
https://www.frontiersin.org/articles/10.3389/fphys.2021.689083/full |
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