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

Autor: D. O. Lopez-Cantu, M. F. Sobral-Reyes, Dario R. Lemos, Reza Abdi, G. U. Ruiz-Esparza, M. Lopez-Marfil, Clemens K. Probst, Krinio Giannikou, J. O. R. Hernandez, Maria Sundberg, M. Vazquez-Segoviano, Elizabeth P. Henske, David J. Kwiatkowski, A. Moran-Horowich, Mustafa Sahin, Xichi Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
congenital
hereditary
and neonatal diseases and abnormalities
Angiomyolipoma
Science
General Physics and Astronomy
Urogenital models
Enzyme-Linked Immunosorbent Assay
Mice
Transgenic
Biology
General Biochemistry
Genetics and Molecular Biology
Article
Tuberous sclerosis
Rats
Nude
Engineering
In vivo
Tuberous Sclerosis Complex 2 Protein
medicine
In Situ Nick-End Labeling
Animals
Humans
Immunoprecipitation
Induced pluripotent stem cell
Cancer models
Kidney
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis
RNA
Disease model
Computational Biology
Cytochromes c
General Chemistry
medicine.disease
Flow Cytometry
Rats
nervous system diseases
Transplantation
Organoids
Disease Models
Animal
Induced pluripotent stem cells
medicine.anatomical_structure
Phosphopyruvate Hydratase
Cancer research
TSC2
Kidney disease
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
Nature Communications
ISSN: 2041-1723
Popis: 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.
The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test new therapies in vivo. Here the authors present a tissue bioengineering strategy for the study of a rare kidney tumor called angiomyolipoma, in vitro and in vivo, using patient-derived hiPSCs.
Databáze: OpenAIRE
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