{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:52:31Z","timestamp":1791931951832,"version":"4.3.4"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK097253"],"award-info":[{"award-number":["R01DK097253"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-20-1-0836"],"award-info":[{"award-number":["W81XWH-20-1-0836"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-20-1-0837"],"award-info":[{"award-number":["W81XWH-20-1-0837"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>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 <jats:italic>in vitro<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/fphys.2021.689083","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T08:23:48Z","timestamp":1622622228000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":55,"title":["Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk"],"prefix":"10.3389","volume":"12","author":[{"given":"Kerstin","family":"Ebefors","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emelie","family":"Lass\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanditha","family":"Anandakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evren U.","family":"Azeloglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse S.","family":"Daehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.bbrc.2018.11.160","article-title":"Induction of steady-state glomeruloid sphere by self-assembly from human embryonic kidney cells","volume":"508","author":"Abe","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1039\/c3lc50350j","article-title":"Microfluidic heart on a chip for higher throughput pharmacological studies","volume":"13","author":"Agarwal","year":"2013","journal-title":"Lab Chip"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/s41581-020-00355-6","article-title":"Kidney tissue engineering for precision medicine","volume":"16","author":"Anandakrishnan","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"ra12","DOI":"10.1126\/scisignal.2004621","article-title":"Interconnected network motifs control podocyte morphology and kidney function","volume":"7","author":"Azeloglu","year":"2014","journal-title":"Sci. Signal."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1159\/000101796","article-title":"Contribution of the endothelium to the glomerular permselectivity barrier in health and disease","volume":"106","author":"Ballermann","year":"2007","journal-title":"Nephron Physiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"S100","DOI":"10.1046\/j.1523-1755.1998.06720.x","article-title":"Shear stress and the endothelium","volume":"67","author":"Ballermann","year":"1998","journal-title":"Kidney Int. Suppl."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"72","DOI":"10.24272\/j.issn.2095-8137.2017.055","article-title":"Kidney disease models: tools to identify mechanisms and potential therapeutic targets","volume":"39","author":"Bao","year":"2018","journal-title":"Zool. Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1093\/ndt\/gft071","article-title":"Animal models of chronic kidney disease: useful but not perfect","volume":"28","author":"Becker","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.yexcr.2017.12.023","article-title":"Liver \u2018organ on a chip\u2019","volume":"363","author":"Beckwitt","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nbt.2989","article-title":"Microfluidic organs-on-chips","volume":"32","author":"Bhatia","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.2337\/db15-1413","article-title":"Atrasentan reduces albuminuria by restoring the glomerular endothelial glycocalyx barrier in diabetic nephropathy","volume":"65","author":"Boels","year":"2016","journal-title":"Diabetes"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.2353\/ajpath.2010.091008","article-title":"PDGF-C mediates glomerular capillary repair","volume":"177","author":"Boor","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.kint.2018.05.003","article-title":"A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell\u2013derived kidney model for drug discovery","volume":"94","author":"Borestr\u00f6m","year":"2018","journal-title":"Kidney Int."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/74166","article-title":"NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome","volume":"24","author":"Boute","year":"2000","journal-title":"Nat. Genet."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1056\/NEJM197804132981507","article-title":"Molecular basis of proteinuria of glomerular origin","volume":"298","author":"Brenner","year":"1978","journal-title":"N. Engl. J. Med."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1681\/ASN.2013070795","article-title":"Glomerular cell cross-talk influences composition and assembly of extracellular matrix","volume":"25","author":"Byron","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1038\/s41467-020-15155-6","article-title":"An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity","volume":"11","author":"Calandrini","year":"2020","journal-title":"Nat. Commun."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12964-020-00605-x","article-title":"The diabetic microenvironment causes mitochondrial oxidative stress in glomerular endothelial cells and pathological crosstalk with podocytes","volume":"18","author":"Casalena","year":"2020","journal-title":"Cell Commun. Signal"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1053\/j.ackd.2013.01.012","article-title":"Renal physiology of pregnancy","volume":"20","author":"Cheung","year":"2013","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fped.2018.00011","article-title":"Basement membrane defects in genetic kidney diseases","volume":"6","author":"Chew","year":"2018","journal-title":"Front. Pediatr."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"327","DOI":"10.3389\/fcell.2020.00327","article-title":"Development of a novel hanging drop platform for engineering controllable 3D microenvironments","volume":"8","author":"Cho","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"F1185","DOI":"10.1152\/ajprenal.00442.2007","article-title":"Preeclamptic sera induce nephrin shedding from podocytes through endothelin-1 release by endothelial glomerular cells","volume":"294","author":"Collino","year":"2008","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13073-019-0615-0","article-title":"Single-cell analysis reveals congruence between kidney organoids and human fetal kidney","volume":"11","author":"Combes","year":"2019","journal-title":"Genome Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"929.e4","DOI":"10.1016\/j.stem.2018.04.022","article-title":"High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping","volume":"22","author":"Czerniecki","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1172\/JCI71195","article-title":"Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis","volume":"124","author":"Daehn","year":"2014","journal-title":"J. Clin. Invest."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3389\/fmed.2018.00076","article-title":"Glomerular endothelial cells stress and cross-talk with podocytes in the development of diabetic kidney disease","volume":"5","author":"Daehn","year":"2018","journal-title":"Front. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"F956","DOI":"10.1152\/ajprenal.00532.2014","article-title":"A microscopic view on the renal endothelial glycocalyx","volume":"308","author":"Dane","year":"2015","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2742","DOI":"10.2337\/db15-1662","article-title":"Hyaluronidase 1 deficiency preserves endothelial function and glycocalyx integrity in early streptozotocin-induced diabetes","volume":"65","author":"Dogne","year":"2016","journal-title":"Diabetes"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.kint.2019.05.007","article-title":"Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells","volume":"96","author":"Ebefors","year":"2019","journal-title":"Kidney Int."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e1005433","DOI":"10.1371\/journal.pcbi.1005433","article-title":"Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability","volume":"13","author":"Falkenberg","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.biocel.2010.05.015","article-title":"The glomerulus\u2013a view from the inside\u2013the endothelial cell","volume":"42","author":"Fogo","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"938","DOI":"10.2353\/ajpath.2008.070416","article-title":"Vascular endothelial growth factor-C, a potential paracrine regulator of glomerular permeability, increases glomerular endothelial cell monolayer integrity and intracellular calcium","volume":"173","author":"Foster","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41563-019-0287-6","article-title":"Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells","volume":"18","author":"Garreta","year":"2019","journal-title":"Nat. Mater."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1681\/ASN.2019121261","article-title":"LIM-nebulette reinforces podocyte structural integrity by linking actin and vimentin filaments","volume":"31","author":"Ge","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41536-020-0093-4","article-title":"Overcoming kidney organoid challenges for regenerative medicine","volume":"5","author":"Geuens","year":"2020","journal-title":"NPJ Regener. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1038\/nm.3405","article-title":"Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in new mouse models with fluorescent lineage tags","volume":"19","author":"Hackl","year":"2013","journal-title":"Nat. Med."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"5167","DOI":"10.1038\/s41467-018-07594-z","article-title":"3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening","volume":"9","author":"Hale","year":"2018","journal-title":"Nat. Commun."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"15961","DOI":"10.1096\/fj.202000724R","article-title":"Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis","volume":"34","author":"Hansen","year":"2020","journal-title":"FASEB J."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1016\/j.bbadis.2017.07.007","article-title":"The relevance of contact-independent cell-to-cell transfer of TDP-43 and SOD1 in amyotrophic lateral sclerosis","volume":"1863","author":"Hanspal","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1097\/MNH.0b013e3283522e7a","article-title":"The glomerular endothelium: new insights on function and structure","volume":"21","author":"Haraldsson","year":"2012","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1152\/physrev.00055.2006","article-title":"Properties of the glomerular barrier and mechanisms of proteinuria","volume":"88","author":"Haraldsson","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/nrneph.2012.19","article-title":"Glomerular hyperfiltration: definitions, mechanisms and clinical implications","volume":"8","author":"Helal","year":"2012","journal-title":"Nat. Rev. Nephrol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.mvr.2003.10.001","article-title":"Electron microscopic evaluation of the endothelial surface layer of glomerular capillaries","volume":"67","author":"Hjalmarsson","year":"2004","journal-title":"Microvasc. Res."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41592-019-0325-y","article-title":"Flow-enhanced vascularization and maturation of kidney organoids in vitro","volume":"16","author":"Homan","year":"2019","journal-title":"Nat. Methods"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1681\/ASN.2012040392","article-title":"Medical costs of CKD in the Medicare population","volume":"24","author":"Honeycutt","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1089\/ten.tec.2013.0446","article-title":"A human in vitro model that mimics the renal proximal tubule","volume":"20","author":"Hoppensack","year":"2014","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"43934","DOI":"10.1038\/srep43934","article-title":"A biomimetic gelatin-based platform elicits a pro-differentiation effect on podocytes through mechanotransduction","volume":"7","author":"Hu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1038\/nprot.2013.137","article-title":"Microfabrication of human organs-on-chips","volume":"8","author":"Huh","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"159ra147","DOI":"10.1126\/scitranslmed.3004249","article-title":"A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice","volume":"4","author":"Huh","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1126\/science.1188302","article-title":"Reconstituting organ-level lung functions on a chip","volume":"328","author":"Huh","year":"2010","journal-title":"Science"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1039\/c3ib40049b","article-title":"Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment","volume":"5","author":"Jang","year":"2013","journal-title":"Integr. Biol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1681\/ASN.2007111205","article-title":"Adriamycin alters glomerular endothelium to induce proteinuria","volume":"20","author":"Jeansson","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1172\/JCI46322","article-title":"Angiopoietin-1 is essential in mouse vasculature during development and in response to injury","volume":"121","author":"Jeansson","year":"2011","journal-title":"J. Clin. Invest."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1097\/00005792-199909000-00005","article-title":"Alport syndrome: an inherited disorder of renal, ocular, and cochlear basement membranes","volume":"78","author":"Kashtan","year":"1999","journal-title":"Medicine"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/S1097-2765(00)80057-X","article-title":"Positionally cloned gene for a novel glomerular protein\u2013nephrin\u2013is mutated in congenital nephrotic syndrome","volume":"1","author":"Kestila","year":"1998","journal-title":"Mol. Cell"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"8487","DOI":"10.1038\/s41598-021-87753-3","article-title":"Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease","volume":"11","author":"Khramova","year":"2021","journal-title":"Sci. Rep."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1039\/c2lc40074j","article-title":"Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow","volume":"12","author":"Kim","year":"2012","journal-title":"Lab Chip"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1039\/c3ib40126j","article-title":"Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation","volume":"5","author":"Kim","year":"2013","journal-title":"Integr. Biol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1002\/stem.2707","article-title":"Gene-edited human kidney organoids reveal mechanisms of disease in podocyte development","volume":"35","author":"Kim","year":"2017","journal-title":"Stem Cells"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1007\/s00018-019-03401-0","article-title":"Stem cell-derived kidney organoids: engineering the vasculature","volume":"77","author":"Koning","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1039\/C8LC00495A","article-title":"Curvature facilitates podocyte culture in a biomimetic platform","volume":"18","author":"Korolj","year":"2018","journal-title":"Lab Chip"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"dev172361","DOI":"10.1242\/dev.172361","article-title":"Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells","volume":"146","author":"Kumar","year":"2019","journal-title":"Development"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"9456","DOI":"10.3390\/ijms21249456","article-title":"Molecular mechanisms in early diabetic kidney disease: glomerular endothelial cell dysfunction","volume":"21","author":"Lassen","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/s41563-020-00853-9","article-title":"Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation","volume":"20","author":"Lawlor","year":"2021","journal-title":"Nat. Mater."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.devcel.2006.09.006","article-title":"Klf2 is an essential regulator of vascular hemodynamic forces in vivo","volume":"11","author":"Lee","year":"2006","journal-title":"Dev. Cell"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.2215\/CJN.11440919","article-title":"Genetic disorders of the glomerular filtration barrier","volume":"15","author":"Li","year":"","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s40620-019-00683-2","article-title":"Assessment of increased glomerular permeability associated with recurrent focal segmental glomerulosclerosis using an in vitro model of the glomerular filtration barrier","volume":"33","author":"Li","year":"","journal-title":"J. Nephrol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejps.2016.02.013","article-title":"Three-dimensional podocyte-endothelial cell co-cultures: assembly, validation, and application to drug testing and intercellular signaling studies","volume":"86","author":"Li","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1097\/MOT.0000000000000174","article-title":"Generating a self-organizing kidney from pluripotent cells","volume":"20","author":"Little","year":"2015","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.semnephrol.2011.06.003","article-title":"Focal and segmental glomerulosclerosis: multiple pathways are involved","volume":"31","author":"Meyrier","year":"2011","journal-title":"Semin. Nephrol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.1039\/C5LC00180C","article-title":"Differentiation of neuroepithelial stem cells into functional dopaminergic neurons in 3D microfluidic cell culture","volume":"15","author":"Moreno","year":"2015","journal-title":"Lab Chip"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1038\/nbt.3392","article-title":"Nephron organoids derived from human pluripotent stem cells model kidney development and injury","volume":"33","author":"Morizane","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.kint.2019.02.013","article-title":"Circulating factors cause proteinuria in parabiotic zebrafish","volume":"96","author":"M\u00fcller-Deile","year":"2019","journal-title":"Kidney Int."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"0069","DOI":"10.1038\/s41551-017-0069","article-title":"Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip","volume":"1","author":"Musah","year":"2017","journal-title":"Nat. Biomed. Eng."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000328010","article-title":"Aging and physiological changes of the kidneys including changes in glomerular filtration rate","volume":"119","author":"Musso","year":"2011","journal-title":"Nephron Physiol."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/s41581-019-0176-x","article-title":"Human kidney organoids: progress and remaining challenges","volume":"15","author":"Nishinakamura","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"F781","DOI":"10.1152\/ajprenal.00621.2012","article-title":"Quantification of the electrostatic properties of the glomerular filtration barrier modeled as a charged fiber matrix separating anionic from neutral Ficoll","volume":"304","author":"\u00d6berg","year":"2013","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/nrneph.2016.127","article-title":"Podocyte-actin dynamics in health and disease","volume":"12","author":"Perico","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"3656","DOI":"10.1038\/s41467-019-11577-z","article-title":"A glomerulus-on-a-chip to recapitulate the human glomerular filtration barrier","volume":"10","author":"Petrosyan","year":"2019","journal-title":"Nat. Commun."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ydbio.2008.01.022","article-title":"Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity","volume":"316","author":"Pozzi","year":"2008","journal-title":"Dev. Biol."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"CJN.19171220","DOI":"10.2215\/cjn.19171220","article-title":"Genetic basis of type IV collagen disorders of the kidney","volume":"13","author":"Quinlan","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-4939-9841-8_11","article-title":"Glomerular endothelial cells: assessment of barrier properties in vitro","volume":"2067","author":"Ramnath","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"e2100031","DOI":"10.1002\/adhm.202100031","article-title":"Multiphoton-guided creation of complex organ-specific microvasculature","author":"Rayner","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1083\/jcb.67.3.638","article-title":"Role of molecular charge in glomerular permeability. Tracer studies with cationized ferritins","volume":"67","author":"Rennke","year":"1975","journal-title":"J. Cell Biol."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1172\/JCI109354","article-title":"Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat","volume":"63","author":"Rennke","year":"1979","journal-title":"J. Clin. Invest."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1038\/s41467-017-02218-4","article-title":"Cell shape information is transduced through tension-independent mechanisms","volume":"8","author":"Ron","year":"2017","journal-title":"Nat. Commun."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"F947","DOI":"10.1152\/ajprenal.90601.2008","article-title":"Glomerular endothelial cell fenestrations: an integral component of the glomerular filtration barrier","volume":"296","author":"Satchell","year":"2009","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1038\/sj.ki.5000277","article-title":"Conditionally immortalized human glomerular endothelial cells expressing fenestrations in response to VEGF","volume":"69","author":"Satchell","year":"2006","journal-title":"Kidney Int."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1007\/s00125-008-0961-8","article-title":"What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium?","volume":"51","author":"Satchell","year":"2008","journal-title":"Diabetologia"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/nm.3843","article-title":"Pharmacological targeting of actin-dependent dynamin oligomerization ameliorates chronic kidney disease in diverse animal models","volume":"21","author":"Schiffer","year":"2015","journal-title":"Nat. Med."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1681\/ASN.2008050549","article-title":"The mesangial cell revisited: no cell is an island","volume":"20","author":"Schlondorff","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1681\/ASN.2015010096","article-title":"Human induced pluripotent stem cell-derived podocytes mature into vascularized glomeruli upon experimental transplantation","volume":"27","author":"Sharmin","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"F40","DOI":"10.1152\/ajprenal.00103.2010","article-title":"High glucose causes dysfunction of the human glomerular endothelial glycocalyx","volume":"300","author":"Singh","year":"2011","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1681\/asn.2007010119","article-title":"Glomerular endothelial glycocalyx constitutes a barrier to protein permeability","volume":"18","author":"Singh","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1681\/ASN.2010030295","article-title":"Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2 signaling","volume":"21","author":"Sison","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"e20802","DOI":"10.1371\/journal.pone.0020802","article-title":"An in vitro model of the glomerular capillary wall using electrospun collagen nanofibres in a bioartificial composite basement membrane","volume":"6","author":"Slater","year":"2011","journal-title":"PLoS One"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1016\/j.biocel.2012.05.020","article-title":"Chronic exposure to laminar shear stress induces Kruppel-like factor 2 in glomerular endothelial cells and modulates interactions with co-cultured podocytes","volume":"44","author":"Slater","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref98","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-021-10128-8","article-title":"Retinoic acid benefits glomerular organotypic differentiation from adult renal progenitor cells in vitro","author":"Sobreiro-Almeida","year":"2021","journal-title":"Stem Cell Rev. Rep."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1046\/j.1523-1755.2001.0600031037.x","article-title":"Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11 chains","volume":"60","author":"St John","year":"2001","journal-title":"Kidney Int."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"e55027","DOI":"10.1371\/journal.pone.0055027","article-title":"Glomerular endothelial cell injury and damage precedes that of podocytes in adriamycin-induced nephropathy","volume":"8","author":"Sun","year":"2013","journal-title":"PLoS One"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1126\/science.2451290","article-title":"Cell and environment interactions in tumor microregions: the multicell spheroid model","volume":"240","author":"Sutherland","year":"1988","journal-title":"Science"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.stem.2013.11.010","article-title":"Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells","volume":"14","author":"Taguchi","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/ncb2894","article-title":"Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney","volume":"16","author":"Takasato","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/nature15695","article-title":"Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis","volume":"526","author":"Takasato","year":"2015","journal-title":"Nature"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.stemcr.2018.08.003","article-title":"Organoids from nephrotic disease-derived iPSCs identify impaired NEPHRIN localization and slit diaphragm formation in kidney podocytes","volume":"11","author":"Tanigawa","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"F1055","DOI":"10.1152\/ajprenal.00621.2011","article-title":"Cross talk between primary human renal tubular cells and endothelial cells in cocultures","volume":"302","author":"Tasnim","year":"2012","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/ki.1993.8","article-title":"Molecular genetics of Alport syndrome","volume":"43","author":"Tryggvason","year":"1993","journal-title":"Kidney Int."},{"key":"ref108","volume-title":"2020 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. United States Renal Data System.","year":"2020"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1152\/nips.01442.2003","article-title":"Tubuloglomerular feedback and the control of glomerular filtration rate","volume":"18","author":"Vallon","year":"2003","journal-title":"News Physiol. Sci."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.stemcr.2018.01.041","article-title":"Renal subcapsular transplantation of PSC-derived kidney organoids induces neo-vasculogenesis and significant glomerular and tubular maturation in vivo","volume":"10","author":"van den Berg","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1681\/ASN.2007040471","article-title":"How do mesangial and endothelial cells form the glomerular tuft?","volume":"19","author":"Vaughan","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1007\/s00467-019-4203-8","article-title":"Nephrotic syndrome in a dish: recent developments in modeling in vitro","volume":"35","author":"Veissi","year":"2020","journal-title":"Pediatr. Nephrol."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrneph.2015.205","article-title":"Exploring the genetic basis of early-onset chronic kidney disease","volume":"12","author":"Vivante","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1177\/0192623318796784","article-title":"Cross talk from tubules to glomeruli","volume":"46","author":"Wang","year":"","journal-title":"Toxicol. Pathol."},{"key":"ref115","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1039\/C7LC00134G","article-title":"A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice","volume":"17","author":"Wang","year":"2017","journal-title":"Lab Chip"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ejphar.2018.01.034","article-title":"Berberine attenuates podocytes injury caused by exosomes derived from high glucose-induced mesangial cells through TGF\u03b21-PI3K\/AKT pathway","volume":"824","author":"Wang","year":"","journal-title":"Eur. J. Pharmacol."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.tibtech.2015.11.001","article-title":"Kidney-on-a-chip technology for drug-induced nephrotoxicity screening","volume":"34","author":"Wilmer","year":"2016","journal-title":"Trends Biotechnol."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1101\/gr.10.12.1903","article-title":"A comparative map of the zebrafish genome","volume":"10","author":"Woods","year":"2000","journal-title":"Genome Res."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"869.e8","DOI":"10.1016\/j.stem.2018.10.010","article-title":"Comparative analysis and refinement of human PSC-derived kidney organoid differentiation with single-cell transcriptomics","volume":"23","author":"Wu","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"9371","DOI":"10.1038\/s41598-017-09907-6","article-title":"Exosomes from high glucose-treated glomerular endothelial cells trigger the epithelial-mesenchymal transition and dysfunction of podocytes","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1242\/bio.015990","article-title":"Exosomes from high glucose-treated glomerular endothelial cells activate mesangial cells to promote renal fibrosis","volume":"5","author":"Wu","year":"2016","journal-title":"Biol. Open"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1038\/ncb2872","article-title":"Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells","volume":"15","author":"Xia","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1021\/acscentsci.9b01097","article-title":"H-FIBER: microfluidic topographical hollow fiber for studies of glomerular filtration barrier","volume":"6","author":"Xie","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref124","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.yexcr.2017.03.026","article-title":"Roles of fluid shear stress and retinoic acid in the differentiation of primary cultured human podocytes","volume":"354","author":"Yang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.kint.2017.06.031","article-title":"Induction of interdigitating cell processes in podocyte culture","volume":"93","author":"Yaoita","year":"2018","journal-title":"Kidney Int."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1681\/ASN.2011121170","article-title":"eNOS deficiency predisposes podocytes to injury in diabetes","volume":"23","author":"Yuen","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref127","doi-asserted-by":"publisher","first-page":"4957","DOI":"10.2147\/Ijn.S110201","article-title":"A nanoporous surface is essential for glomerular podocyte differentiation in three-dimensional culture","volume":"11","author":"Zennaro","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"F41","DOI":"10.1152\/ajprenal.00069.2020","article-title":"Open microfluidic coculture reveals paracrine signaling from human kidney epithelial cells promotes kidney specificity of endothelial cells","volume":"319","author":"Zhang","year":"2020","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.1681\/ASN.2006070798","article-title":"Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice","volume":"17","author":"Zhao","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/ki.2014.286","article-title":"Reduced Kruppel-like factor 2 expression may aggravate the endothelial injury of diabetic nephropathy","volume":"87","author":"Zhong","year":"2014","journal-title":"Kidney Int."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"31771","DOI":"10.1038\/srep31771","article-title":"Development of a functional glomerulus at the organ level on a chip to mimic hypertensive nephropathy","volume":"6","author":"Zhou","year":"2016","journal-title":"Sci. Rep."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1681\/ASN.2011080776","article-title":"Inducible podocyte injury and proteinuria in transgenic zebrafish","volume":"23","author":"Zhou","year":"2012","journal-title":"J. Am. Soc. Nephrol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.689083\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T08:23:52Z","timestamp":1622622232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.689083\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,2]]},"references-count":132,"alternative-id":["10.3389\/fphys.2021.689083"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.689083","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,2]]},"article-number":"689083"}}