ArticleJournal of the American Society of Nephrology : JASN2020
Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for Cystinosis.
Article in Journal of the American Society of Nephrology : JASN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- Kidney organoids as models for hereditary kidney diseases: Toward precision medicine (Review).Experimental and therapeutic medicine · 2026Review
- Exfoliated kidney cells from urine for non-invasive kidney transplant monitoring: A potential opportunity?Clinical and experimental nephrology · 2026Review
- Advances in Pharmacological Treatments for Cystinosis: Cysteamine and Its Alternatives.ACS pharmacology & translational science · 2026Review
- A Refined Method for Micro-Scale Blood Cystine Measurement in Preclinical Cystinosis Models.International journal of molecular sciences · 2026Article
- Cystinosis and Cellular Energy Failure: Mitochondria at the Crossroads.International journal of molecular sciences · 2026Review
- Organoids in Genetic Disorders: from Disease Modeling to Translational Applications.Stem cell reviews and reports · 2025Review
- Kidney Organoids: Current Advances and Applications.Life (Basel, Switzerland) · 2025Review
- JIP4 deficiency causes a lysosomal storage disease arising from impaired cystine efflux.bioRxiv : the preprint server for biology · 2025Article
- Biomedical applications of organoids in genetic diseases.Medical review (2021) · 2025Review
- Review
- Article
- Emerging therapeutic strategies for cystinosis.Frontiers in pediatrics · 2025Review
- Advances in Diagnosis and Treatment of Inherited Kidney Diseases in Children.Kidney diseases (Basel, Switzerland) · 2024Review
- Advances and potential of regenerative medicine in pediatric nephrology.Pediatric nephrology (Berlin, Germany) · 2024Review
- Evaluation of the efficacy of cystinosin supplementation through CTNS mRNA delivery in experimental models for cystinosis.Scientific reports · 2023Article
- Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.Scientific reports · 2023Article
- An integrated organoid omics map extends modeling potential of kidney disease.Nature communications · 2023Article
- Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization.Nature communications · 2023Article
- The role of lysosomes in metabolic and autoimmune diseases.Nature reviews. Nephrology · 2023Review
- Kidney Organoid Derived from Human Pluripotent and Adult Stem Cells for Disease Modeling.Development & reproduction · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in
methodsTo address a lack of good human-based cell culture models for studying cystinosis, we generated the first human induced pluripotent stem cell (iPSC) and kidney organoid models of the disorder. We used a variety of techniques to examine hallmarks of cystinosis-including cystine accumulation, lysosome size, the autophagy pathway, and apoptosis-and performed RNA sequencing on isogenic lines to identify differentially expressed genes in the cystinosis models compared with controls.
resultsCompared with controls, these cystinosis models exhibit elevated cystine levels, increased apoptosis, and defective basal autophagy. Cysteamine treatment ameliorates this phenotype, except for abnormalities in apoptosis and basal autophagy. We found that treatment with everolimus, an inhibitor of the mTOR pathway, reduces the number of large lysosomes, decreases apoptosis, and activates autophagy, but it does not rescue the defect in cystine loading. However, dual treatment of cystinotic iPSCs or kidney organoids with cysteamine and everolimus corrects all of the observed phenotypic abnormalities.
conclusionsThese observations suggest that combination therapy with a cystine-depleting drug such as cysteamine and an mTOR pathway inhibitor such as everolimus has potential to improve treatment of cystinosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.