{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T18:48:28Z","timestamp":1789325308625,"version":"build-2803163510"},"reference-count":130,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wesco Scientific Promotion Foundation and the Japanese Society for the Promotion of Science (JSPS)\/Grant-in-Aid for Scientific Research","award":["24K11411"],"award-info":[{"award-number":["24K11411"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Kidney organoids, derived from stem cells, including pluripotent stem cells and adult progenitor cells, have been reported as three-dimensional in vitro models that reflect key aspects of kidney development, structure, and function. Advances in differentiation protocols and tissue engineering have enabled the generation of organoids that exhibit nephron-like structures, including glomerular and tubular structures. Kidney organoids have been widely applied in several directions, including disease modeling and therapeutic screening, drug nephrotoxicity evaluation, and regenerative medicine. In particular, kidney organoids offer a promising platform for studying genetic kidney diseases, such as polycystic kidney disease and congenital anomalies of the kidney and urinary tract (CAKUT), by allowing patient-specific modeling for the analysis of pathophysiology and therapeutic screening. Despite several current limitations, such as incomplete maturation, lack of full nephron segmentation, and variability between protocols and cell conditions, further technological innovations such as microfluidics and bioengineering may refine kidney organoid systems. This review highlights recent advances in kidney organoid research, outlines major applications, and discusses future directions to enhance their physiological relevance, functional maturity, and translational integration into preclinical and clinical nephrology.<\/jats:p>","DOI":"10.3390\/life15111680","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"1680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Kidney Organoids: Current Advances and Applications"],"prefix":"10.3390","volume":"15","author":[{"given":"Hiroyuki","family":"Nakanoh","sequence":"first","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5442-7008","authenticated-orcid":false,"given":"Kenji","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naruhiko","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Haraguchi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan"},{"name":"Department of Nephrology, Aoe Clinic, 5-1-3, Aoe, Okayama 700-0941, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1468-5170","authenticated-orcid":false,"given":"Jun","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"929","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":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nmat4994","article-title":"Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease","volume":"16","author":"Cruz","year":"2017","journal-title":"Nat. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.molmed.2017.01.001","article-title":"Kidney Organoids: A Translational Journey","volume":"23","author":"Morizane","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8715","DOI":"10.1038\/ncomms9715","article-title":"Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids","volume":"6","author":"Freedman","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","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":"ref_9","doi-asserted-by":"crossref","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":"ref_10","doi-asserted-by":"crossref","first-page":"5462","DOI":"10.1038\/s41467-019-13382-0","article-title":"Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation","volume":"10","author":"Subramanian","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"869","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":"ref_12","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.devcel.2010.04.008","article-title":"Patterning a complex organ: Branching morphogenesis and nephron segmentation in kidney development","volume":"18","author":"Costantini","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4161\/psb.5.1.10119","article-title":"Tissue-type specific systemin perception and the elusive systemin receptor","volume":"5","author":"Hind","year":"2010","journal-title":"Plant Signal Behav."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Little, M.H., and McMahon, A.P. (2012). Mammalian kidney development: Principles, progress, and projections. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a008300"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1242\/dev.124.20.4077","article-title":"Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium","volume":"124","author":"Sainio","year":"1997","journal-title":"Development"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1242\/dev.119.4.1005","article-title":"Expression of the c-ret proto-oncogene during mouse embryogenesis","volume":"119","author":"Pachnis","year":"1993","journal-title":"Development"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.stem.2008.05.020","article-title":"Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development","volume":"3","author":"Kobayashi","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.devcel.2005.05.016","article-title":"Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system","volume":"9","author":"Carroll","year":"2005","journal-title":"Dev. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.devcel.2015.06.021","article-title":"A synthetic niche for nephron progenitor cells","volume":"34","author":"Brown","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kiefer, S.M., Robbins, L., and Rauchman, M. (2012). Conditional expression of Wnt9b in Six2-positive cells disrupts stomach and kidney function. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043098"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1101\/gad.9.22.2795","article-title":"A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye","volume":"9","author":"Dudley","year":"1995","journal-title":"Genes. Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1242\/dev.01944","article-title":"FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons","volume":"132","author":"Grieshammer","year":"2005","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.devcel.2012.04.018","article-title":"FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man","volume":"22","author":"Barak","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1242\/dev.02773","article-title":"Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron","volume":"134","author":"Cheng","year":"2007","journal-title":"Development"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ydbio.2007.08.021","article-title":"Cessation of renal morphogenesis in mice","volume":"310","author":"Hartman","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","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":"ref_27","doi-asserted-by":"crossref","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":"ref_28","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1242\/dev.104802","article-title":"The origin of the mammalian kidney: Implications for recreating the kidney in vitro","volume":"142","author":"Takasato","year":"2015","journal-title":"Development"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/stem.1891","article-title":"Single adult kidney stem\/progenitor cells reconstitute three-dimensional nephron structures in vitro","volume":"33","author":"Kitamura","year":"2015","journal-title":"Stem Cells"},{"key":"ref_30","doi-asserted-by":"crossref","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":"Ritsma","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","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":"ref_32","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1681\/ASN.2017080887","article-title":"Conserved and Divergent Features of Human and Mouse Kidney Organogenesis","volume":"29","author":"Lindstrom","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","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":"ref_34","doi-asserted-by":"crossref","unstructured":"Formica, C., Addario, G., Fagiolino, S., Moroni, L., and Mota, C. (2025). Microfluidic bioprinting as a tool to produce hiPSCs-derived renal organoids. Biofabrication, 17.","DOI":"10.1088\/1758-5090\/addb7e"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s40580-021-00285-4","article-title":"Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip","volume":"8","author":"Lee","year":"2021","journal-title":"Nano Converg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"dmm050113","DOI":"10.1242\/dmm.050113","article-title":"A systematic review of kidney-on-a-chip-based models to study human renal (patho-)physiology","volume":"16","author":"Nguyen","year":"2023","journal-title":"Dis. Model. Mech."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Huang, W., Chen, Y.Y., He, F.F., and Zhang, C. (2024). Revolutionizing nephrology research: Expanding horizons with kidney-on-a-chip and beyond. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1373386"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bas-Cristobal Menendez, A., Du, Z., van den Bosch, T.P.P., Othman, A., Gaio, N., Silvestri, C., Quiros, W., Lin, H., Korevaar, S., and Merino, A. (2022). Creating a kidney organoid-vasculature interaction model using a novel organ-on-chip system. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-24945-5"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.stem.2019.06.009","article-title":"Generation of Human PSC-Derived Kidney Organoids with Patterned Nephron Segments and a De Novo Vascular Network","volume":"25","author":"Low","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12468","DOI":"10.3389\/ti.2024.12468","article-title":"Interactions of the Immune System with Human Kidney Organoids","volume":"37","author":"Shankar","year":"2024","journal-title":"Transpl. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13287-024-03739-8","article-title":"Monocytes prevent apoptosis of iPSCs and promote differentiation of kidney organoids","volume":"15","author":"Pecksen","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Pahuja, A., Goux Corredera, I., Moya-Rull, D., Garreta, E., and Montserrat, N. (2024). Engineering physiological environments to advance kidney organoid models from human pluripotent stem cells. Curr. Opin. Cell Biol., 86.","DOI":"10.1016\/j.ceb.2023.102306"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41378-020-00185-3","article-title":"Microtechnology-based methods for organoid models","volume":"6","author":"Velasco","year":"2020","journal-title":"Microsyst. Nanoeng."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hong, S., Song, M., Miyoshi, T., Morizane, R., Bonventre, J.V., and Lee, L.P. (2024). Dynamic Kidney Organoid Microphysiological Analysis Platform. bioRxiv.","DOI":"10.1101\/2024.10.27.620552"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.cmet.2022.04.009","article-title":"A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells","volume":"34","author":"Garreta","year":"2022","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2022.06.012","article-title":"Kidney organoids: A pioneering model for kidney diseases","volume":"250","author":"Tekguc","year":"2022","journal-title":"Transl. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, M., Cardilla, A., Ngeow, J., Gong, X., and Xia, Y. (2022). Studying Kidney Diseases Using Organoid Models. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.845401"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1681\/ASN.0000000647","article-title":"Genotype-Based Molecular Mechanisms in Alport Syndrome","volume":"36","author":"Caparali","year":"2025","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Zheng, Q., and Xie, J. (2024). Exploration of Gene Therapy for Alport Syndrome. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061159"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hirayama, R., Toyohara, K., Watanabe, K., Otsuki, T., Araoka, T., Mae, S.I., Horinouchi, T., Yamamura, T., Okita, K., and Hotta, A. (2023). iPSC-derived type IV collagen alpha5-expressing kidney organoids model Alport syndrome. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05203-4"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1111\/gtc.13170","article-title":"Investigation of exon skipping therapy in kidney organoids from Alport syndrome patients derived iPSCs","volume":"29","author":"Yabuuchi","year":"2024","journal-title":"Genes. Cells"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1038\/s41431-020-0642-8","article-title":"Genetic aspects of congenital nephrotic syndrome: A consensus statement from the ERKNet-ESPN inherited glomerulopathy working group","volume":"28","author":"Ozaltin","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","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":"ref_54","doi-asserted-by":"crossref","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":"ref_55","doi-asserted-by":"crossref","first-page":"dev200198","DOI":"10.1242\/dev.200198","article-title":"Human pluripotent stem cell-derived kidney organoids for personalized congenital and idiopathic nephrotic syndrome modeling","volume":"149","author":"Jansen","year":"2022","journal-title":"Development"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1681\/ASN.2022060707","article-title":"Kidney Organoids Generated Using an Allelic Series of NPHS2 Point Variants Reveal Distinct Intracellular Podocin Mistrafficking","volume":"34","author":"Dorison","year":"2023","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2308556","DOI":"10.1002\/advs.202308556","article-title":"Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development","volume":"11","author":"Wang","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","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":"ref_59","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","article-title":"Autosomal dominant polycystic kidney disease","volume":"369","author":"Torres","year":"2007","journal-title":"Lancet"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/ki.2014.120","article-title":"Analysis of data from the ERA-EDTA Registry indicates that conventional treatments for chronic kidney disease do not reduce the need for renal replacement therapy in autosomal dominant polycystic kidney disease","volume":"86","author":"Spithoven","year":"2014","journal-title":"Kidney Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1681\/ASN.2020030378","article-title":"PKD1-Dependent Renal Cystogenesis in Human Induced Pluripotent Stem Cell-Derived Ureteric Bud\/Collecting Duct Organoids","volume":"31","author":"Kuraoka","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.bbrc.2020.06.141","article-title":"A novel ADPKD model using kidney organoids derived from disease-specific human iPSCs","volume":"529","author":"Shimizu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Facioli, R., Lojudice, F.H., Anauate, A.C., Maquigussa, E., Nishiura, J.L., Heilberg, I.P., Sogayar, M.C., and Boim, M.A. (2021). Kidney organoids generated from erythroid progenitors cells of patients with autosomal dominant polycystic kidney disease. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252156"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Linn, A.K., Maneepitasut, W., Tubsuwan, A., Kitiyanant, N., Phakdeekitcharoen, B., Borwornpinyo, S., Hongeng, S., and Phanthong, P. (2022). Establishment and Characterization of MUi027-A: A Novel Patient-Derived Cell Line of Polycystic Kidney Disease with PKD1 Mutation. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050766"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113431","DOI":"10.1016\/j.celrep.2023.113431","article-title":"Human iPSC-derived renal collecting duct organoid model cystogenesis in ADPKD","volume":"42","author":"Mae","year":"2023","journal-title":"Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.stem.2024.03.005","article-title":"Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease","volume":"31","author":"Vishy","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, J., Qiu, Y., Zhang, L., Zhou, X., Hu, S., Liu, Q., Yin, S., Su, Z., Liu, S., and Liu, H. (2024). Adenine base editor corrected ADPKD point mutations in hiPSCs and kidney organoids. Adv. Biotechnol., 2.","DOI":"10.1007\/s44307-024-00026-8"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Scarlat, A., Trionfini, P., Rizzo, P., Conti, S., Longaretti, L., Breno, M., Longhi, L., Xinaris, C., Remuzzi, G., and Benigni, A. (2025). PKD1 mutation perturbs morphogenesis in tubular epithelial organoids derived from human pluripotent stem cells. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-94855-9"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7918","DOI":"10.1038\/s41467-022-35537-2","article-title":"Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.stem.2022.06.005","article-title":"A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery","volume":"29","author":"Tran","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.stem.2024.04.002","article-title":"Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease","volume":"31","author":"Huang","year":"2024","journal-title":"Cell Stem Cell"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Koslowski, S., Latapy, C., Auvray, P., Blondel, M., and Meijer, L. (2020). An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini-Pigs. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124537"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1053\/j.ajkd.2025.05.015","article-title":"Autosomal Dominant Tubulointerstitial Kidney Disease: A Review","volume":"86","author":"Bleyer","year":"2025","journal-title":"Am. J. Kidney Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/ndt\/gfab268","article-title":"Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease","volume":"38","author":"Mabillard","year":"2023","journal-title":"Nephrol. Dial. Transpl. Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41572-019-0109-9","article-title":"Autosomal dominant tubulointerstitial kidney disease","volume":"5","author":"Devuyst","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1186\/s13023-025-03951-6","article-title":"Autosomal dominant tubulointerstitial kidney disease-UMOD: A short review","volume":"20","author":"Qiao","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e180347","DOI":"10.1172\/JCI180347","article-title":"Disrupted uromodulin trafficking is rescued by targeting TMED cargo receptors","volume":"134","author":"Brown","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ng.2543","article-title":"Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing","volume":"45","author":"Kirby","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cell.2019.07.002","article-title":"Small Molecule Targets TMED9 and Promotes Lysosomal Degradation to Reverse Proteinopathy","volume":"178","author":"Emani","year":"2019","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s00467-018-4188-8","article-title":"HNF1B nephropathy has a slow-progressive phenotype in childhood-with the exception of very early onset cases: Results of the German Multicenter HNF1B Childhood Registry","volume":"34","author":"Okorn","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.stemcr.2024.04.011","article-title":"Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations","volume":"19","author":"Bantounas","year":"2024","journal-title":"Stem Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1177\/000992288602500206","article-title":"Familial juvenile nephronophthisis. A review and differential diagnosis","volume":"25","author":"Cantani","year":"1986","journal-title":"Clin. Pediatr."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Arai, Y., Ito, H., Shimizu, T., Shimoda, Y., Song, D., Matsuo-Takasaki, M., Hayata, T., and Hayashi, Y. (2024). Patient-derived and gene-edited pluripotent stem cells lacking NPHP1 recapitulate juvenile nephronophthisis in abnormalities of primary cilia and renal cyst formation. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1370723"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1056\/NEJM196705252762101","article-title":"Enzymatic defect in Fabry\u2019s disease. Ceramidetrihexosidase deficiency","volume":"276","author":"Brady","year":"1967","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1038\/s12276-021-00683-y","article-title":"Human kidney organoids reveal the role of glutathione in Fabry disease","volume":"53","author":"Kim","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12967-023-03992-0","article-title":"Modeling of Fabry disease nephropathy using patient derived human induced pluripotent stem cells and kidney organoid system","volume":"21","author":"Cui","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.trsl.2023.02.005","article-title":"CRISPR\/Cas9-mediated A4GALT suppression rescues Fabry disease phenotypes in a kidney organoid model","volume":"258","author":"Cui","year":"2023","journal-title":"Transl. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/hmg\/ddh152","article-title":"Molecular pathogenesis of cystinosis: Effect of CTNS mutations on the transport activity and subcellular localization of cystinosin","volume":"13","author":"Kalatzis","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1681\/ASN.2019070712","article-title":"Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine\/mTOR Inhibition Combination Therapy for Cystinosis","volume":"31","author":"Hollywood","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41581-024-00818-0","article-title":"Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: A consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group","volume":"20","author":"Mekahli","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6496","DOI":"10.1038\/s41467-021-26596-y","article-title":"A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo","volume":"12","author":"Hernandez","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"111048","DOI":"10.1016\/j.celrep.2022.111048","article-title":"Renal organoid modeling of tuberous sclerosis complex reveals lesion features arise from diverse developmental processes","volume":"40","author":"Pietrobon","year":"2022","journal-title":"Cell Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2147\/IJNRD.S103784","article-title":"Rodent models of diabetic nephropathy: Their utility and limitations","volume":"9","author":"Kitada","year":"2016","journal-title":"Int. J. Nephrol. Renov. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.tibtech.2019.12.010","article-title":"Bioengineered 3D Models to Recapitulate Tissue Fibrosis","volume":"38","author":"Sacchi","year":"2020","journal-title":"Trends Biotechnol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1042\/EBC20200158","article-title":"Bioprinting of kidney in vitro models: Cells, biomaterials, and manufacturing techniques","volume":"65","author":"Fransen","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.addr.2013.12.002","article-title":"Tissue-engineered kidney disease models","volume":"69\u201370","author":"Desrochers","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"C151","DOI":"10.1152\/ajpcell.00120.2020","article-title":"A brief history of organoids","volume":"319","author":"Corro","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"100336","DOI":"10.1016\/j.labinv.2024.100336","article-title":"Bile Acid Receptor Agonist Reverses Transforming Growth Factor-beta1-Mediated Fibrogenesis in Human Induced Pluripotent Stem Cells-Derived Kidney Organoids","volume":"104","author":"Yang","year":"2024","journal-title":"Lab. Investig."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41587-019-0048-8","article-title":"Tubuloids derived from human adult kidney and urine for personalized disease modeling","volume":"37","author":"Schutgens","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.gendis.2021.01.003","article-title":"Kidney organoids as a promising tool in nephrology","volume":"9","author":"Wu","year":"2022","journal-title":"Genes. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e2403230","DOI":"10.1002\/adhm.202403230","article-title":"Kidney Fibrosis In Vitro and In Vivo Models: Path Toward Physiologically Relevant Humanized Models","volume":"14","author":"Addario","year":"2025","journal-title":"Adv. Health Healthc. Mater."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Susa, K., Kobayashi, K., Galichon, P., Matsumoto, T., Tamura, A., Hiratsuka, K., Gupta, N.R., Yazdi, I.K., Bonventre, J.V., and Morizane, R. (2023). ATP\/ADP biosensor organoids for drug nephrotoxicity assessment. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1138504"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacbts.2019.10.008","article-title":"Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach?","volume":"4","year":"2019","journal-title":"JACC Basic. Transl. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Romero-Guevara, R., Ioannides, A., and Xinaris, C. (2020). Kidney Organoids as Disease Models: Strengths, Weaknesses and Perspectives. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.563981"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"105705","DOI":"10.1016\/j.yrtph.2024.105705","article-title":"The new paradigm in animal testing\u2014\u201c3Rs alternatives\u201d","volume":"153","author":"Poh","year":"2024","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Musah, S., Mammoto, A., Ferrante, T.C., Jeanty, S.S.F., Hirano-Kobayashi, M., Mammoto, T., Roberts, K., Chung, S., Novak, R., and Ingram, M. (2017). Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nat. Biomed. Eng., 1.","DOI":"10.1038\/s41551-017-0069"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1631\/jzus.B2100701","article-title":"High-throughput \u201cread-on-ski\u201d automated imaging and label-free detection system for toxicity screening of compounds using personalised human kidney organoids","volume":"23","author":"Wang","year":"2022","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Oishi, H., Tabibzadeh, N., and Morizane, R. (2024). Advancing preclinical drug evaluation through automated 3D imaging for high-throughput screening with kidney organoids. Biofabrication, 16.","DOI":"10.1088\/1758-5090\/ad38df"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1293\/tox.2022-0006","article-title":"Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model","volume":"35","author":"Ueno","year":"2022","journal-title":"J. Toxicol. Pathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1159\/000544795","article-title":"Supplement-Induced Acute Kidney Injury Reproduced in Kidney Organoids","volume":"56","author":"Nakanoh","year":"2025","journal-title":"Am. J. Nephrol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Roye, Y., Bhattacharya, R., Mou, X., Zhou, Y., Burt, M.A., and Musah, S. (2021). A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium. Micromachines, 12.","DOI":"10.3390\/mi12080967"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Scarlat, A., Tomasoni, S., and Trionfini, P. (2025). Autosomal Dominant Polycystic Kidney Disease: From Pathogenesis to Organoid Disease Models. Biomedicines, 13.","DOI":"10.3390\/biomedicines13071766"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Matsui, K., Yamanaka, S., Chen, S., Matsumoto, N., Morimoto, K., Kinoshita, Y., Inage, Y., Saito, Y., Takamura, T., and Fujimoto, T. (2023). Long-term viable chimeric nephrons generated from progenitor cells are a reliable model in cisplatin-induced toxicity. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05484-9"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Fujimori, K., Yamanaka, S., Shimada, K., Matsui, K., Kawagoe, S., Kuroda, T., Ikeda, A., Inoue, M., Kobayashi, E., and Yokoo, T. (2024). Generation of human-pig chimeric renal organoids using iPSC technology. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06986-w"},{"key":"ref_115","doi-asserted-by":"crossref","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 Regen. Med."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Li, C., An, N., Song, Q., Hu, Y., Yin, W., Wang, Q., Le, Y., Pan, W., Yan, X., and Wang, Y. (2024). Enhancing organoid culture: Harnessing the potential of decellularized extracellular matrix hydrogels for mimicking microenvironments. J. Biomed. Sci., 31.","DOI":"10.1186\/s12929-024-01086-7"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e2103526","DOI":"10.1002\/advs.202103526","article-title":"Kidney Decellularized Extracellular Matrix Enhanced the Vascularization and Maturation of Human Kidney Organoids","volume":"9","author":"Kim","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41592-018-0253-2","article-title":"Evaluation of variability in human kidney organoids","volume":"16","author":"Phipson","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ajpath.2022.01.009","article-title":"Human Kidney Organoids and Tubuloids as Models of Complex Kidney Disease","volume":"192","author":"Combes","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_120","first-page":"525","article-title":"AI-enabled organoids: Construction, analysis, and application","volume":"31","author":"Bai","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Matthews, J.M., Schuster, B., Kashaf, S.S., Liu, P., Ben-Yishay, R., Ishay-Ronen, D., Izumchenko, E., Shen, L., Weber, C.R., and Bielski, M. (2022). OrganoID: A versatile deep learning platform for tracking and analysis of single-organoid dynamics. PLoS Comput. Biol., 18.","DOI":"10.1101\/2022.01.13.476248"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Spiller, E.R., Ung, N., Kim, S., Patsch, K., Lau, R., Strelez, C., Doshi, C., Choung, S., Choi, B., and Juarez Rosales, E.F. (2021). Imaging-Based Machine Learning Analysis of Patient-Derived Tumor Organoid Drug Response. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.771173"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Liu, X., Shi, J., Jiao, Y., An, J., Tian, J., Yang, Y., and Zhuo, L. (2024). Integrated multi-omics with machine learning to uncover the intricacies of kidney disease. Brief. Bioinform., 25.","DOI":"10.1093\/bib\/bbae364"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1038\/s41467-023-39740-7","article-title":"An integrated organoid omics map extends modeling potential of kidney disease","volume":"14","author":"Lasse","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e2219699120","DOI":"10.1073\/pnas.2219699120","article-title":"A single-cell multiomic analysis of kidney organoid differentiation","volume":"120","author":"Yoshimura","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e175824","DOI":"10.1172\/JCI175824","article-title":"FDA Modernization Act 2.0: Transitioning beyond animal models with human cells, organoids, and AI\/ML-based approaches","volume":"133","author":"Zushin","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1186\/s13287-022-02950-9","article-title":"Organoids: A systematic review of ethical issues","volume":"13","author":"Massey","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12152-023-09532-3","article-title":"The Ethics of Human Brain Organoid Transplantation in Animals","volume":"16","author":"Kataoka","year":"2023","journal-title":"Neuroethics"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.stem.2023.07.011","article-title":"Advances and challenges toward developing kidney organoids for clinical applications","volume":"30","author":"Nishinakamura","year":"2023","journal-title":"Cell Stem Cell"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Mollaki, V. (2021). Ethical Challenges in Organoid Use. BioTech, 10.","DOI":"10.3390\/biotech10030012"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:57:45Z","timestamp":1761760665000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/11\/1680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":130,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["life15111680"],"URL":"https:\/\/doi.org\/10.3390\/life15111680","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]}}}