Engineered Kidney Tubules for Modeling Patient-Specific Diseases and Drug Discovery.
EBioMedicine
; 33: 253-268, 2018 Jul.
Article
en En
| MEDLINE
| ID: mdl-30049385
The lack of engineering systems able to faithfully reproduce complex kidney structures in vitro has made it difficult to efficiently model kidney diseases and development. Using polydimethylsiloxane (PDMS) scaffolds and a kidney-derived cell line we developed a system to rapidly engineer custom-made 3D tubules with typical renal epithelial properties. This system was successfully employed to engineer patient-specific tubules, to model polycystic kidney disease (PKD) and test drug efficacy, and to identify a potential new pharmacological treatment. By optimizing our system we constructed functional ureteric bud (UB)-like tubules from human induced pluripotent stem cells (iPSCs), and identified a combination of growth factors that induces budding morphogenesis like embryonic kidneys do. Finally, we applied this assay to investigate budding defects in UB-like tubules derived from a patient with a PAX2 mutation. Our system enables the modeling of human kidney disease and development, drug testing and discovery, and lays the groundwork for engineering anatomically correct kidney tissues in vitro and developing personalized medicine applications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Técnicas de Cultivo de Órganos
/
Factor de Transcripción PAX2
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Células Madre Pluripotentes Inducidas
/
Enfermedades Renales Poliquísticas
/
Túbulos Renales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
EBioMedicine
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Países Bajos