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Updated: Oct 13, 2025
Isogenic Kidney Glomerulus Chip Engineered from Human Induced Pluripotent Stem Cells
Published on: November 4, 2022
A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo
J O R Hernandez1, X Wang1, M Vazquez-Segoviano1
1Renal Division, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Abstract:
The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2-/- hiPSCs but not from isogenic TSC2+/- or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2-/- renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.
Insights
Researchers developed kidney organoids from Tuberous Sclerosis Complex (TSC) patient cells to model rare kidney tumors (angiomyolipomas). This approach enables in vivo study and testing of new therapies for TSC-associated kidney disease.
Area of Science:
- Biomedical Engineering
- Nephrology
- Genetics
Background:
- Limited animal models hinder understanding of rare kidney diseases like Tuberous Sclerosis Complex (TSC).
- TSC is associated with kidney tumors called angiomyolipomas (AML) and epithelial cysts.
- Existing mouse models do not fully recapitulate TSC-associated kidney pathologies.
Purpose of the Study:
- To develop a novel in vivo model for TSC-associated kidney disease using patient-derived organoids.
- To investigate the disease mechanisms of kidney angiomyolipomas (AML) in a relevant model.
- To test the efficacy of targeted therapies for TSC-related kidney lesions.
Main Methods:
- Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived induced pluripotent stem cells (hiPSCs).
- Characterization of organoids for transcriptional signature and cell phenotype mirroring human kidney AMLs.
- Transplantation of TSC2-deficient renal organoids into immunodeficient rats for in vivo modeling.
- Evaluation of rapamycin-loaded nanoparticles for AML ablation in the transplanted organoid model.
Main Results:
- TSC2-deficient hiPSC-derived kidney organoids recapitulated the transcriptional signature and myomelanocytic phenotype of human kidney AMLs.
- Organoids developed epithelial cysts, mimicking key TSC-associated kidney lesions.
- Transplanted TSC2-deficient renal organoids successfully modeled AML in vivo.
- Rapamycin-loaded nanoparticles demonstrated efficacy in ablating AMLs within the organoid model.
Conclusions:
- Patient-derived kidney organoids provide a scalable and innovative in vivo model for rare kidney diseases like TSC.
- This model system effectively replicates TSC-associated kidney tumors and cysts, offering new avenues for mechanistic studies.
- The study demonstrates the potential of bioengineered organoids for preclinical testing of targeted therapies for rare kidney diseases.
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