Bioengineered models of Parkinson's disease using patient-derived dopaminergic neurons exhibit distinct biological profiles in a 3D microenvironment.
Cell Mol Life Sci
; 79(2): 78, 2022 Jan 19.
Article
en En
| MEDLINE
| ID: mdl-35044538
ABSTRACT
Three-dimensional (3D) in vitro culture systems using human induced pluripotent stem cells (hiPSCs) are useful tools to model neurodegenerative disease biology in physiologically relevant microenvironments. Though many successful biomaterials-based 3D model systems have been established for other neurogenerative diseases, such as Alzheimer's disease, relatively few exist for Parkinson's disease (PD) research. We employed tissue engineering approaches to construct a 3D silk scaffold-based platform for the culture of hiPSC-dopaminergic (DA) neurons derived from healthy individuals and PD patients harboring LRRK2 G2019S or GBA N370S mutations. We then compared results from protein, gene expression, and metabolic analyses obtained from two-dimensional (2D) and 3D culture systems. The 3D platform enabled the formation of dense dopamine neuronal network architectures and developed biological profiles both similar and distinct from 2D culture systems in healthy and PD disease lines. PD cultures developed in 3D platforms showed elevated levels of α-synuclein and alterations in purine metabolite profiles. Furthermore, computational network analysis of transcriptomic networks nominated several novel molecular interactions occurring in neurons from patients with mutations in LRRK2 and GBA. We conclude that the brain-like 3D system presented here is a realistic platform to interrogate molecular mechanisms underlying PD biology.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Neuronas Dopaminérgicas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Mol Life Sci
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos