A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo

Nat Commun. 2021 Nov 11;12(1):6496. doi: 10.1038/s41467-021-26596-y.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Computational Biology
  • Cytochromes c / metabolism
  • Disease Models, Animal
  • Engineering
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunoprecipitation
  • In Situ Nick-End Labeling
  • Induced Pluripotent Stem Cells / metabolism
  • Male
  • Mice, Transgenic
  • Organoids / metabolism
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / metabolism*
  • Rats
  • Rats, Nude
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Tuberous Sclerosis Complex 2 Protein / genetics
  • Tuberous Sclerosis Complex 2 Protein / metabolism*


  • Tsc2 protein, rat
  • Tuberous Sclerosis Complex 2 Protein
  • Cytochromes c
  • Phosphopyruvate Hydratase