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Sci Rep ; 10(1): 15469, 2020 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-32963285

RESUMEN

Mechanical forces are important in the regulation of physiological homeostasis and the development of disease. The application of mechanical forces to cultured cells is often performed using specialized systems that lack the flexibility and throughput of other biological techniques. In this study, we developed a high throughput platform for applying complex dynamic mechanical forces to cultured cells. We validated the system for its ability to accurately apply parallel mechanical stretch in a 96 well plate format in 576 well simultaneously. Using this system, we screened for optimized conditions to stimulate increases in Oct-4 and other transcription factor expression in mouse fibroblasts. Using high throughput mechanobiological screening assays, we identified small molecules that can synergistically enhance the increase in reprograming-related gene expression in mouse fibroblasts when combined with mechanical loading. Taken together, our findings demonstrate a new powerful tool for investigating the mechanobiological mechanisms of disease and performing drug screening in the presence of applied mechanical load.


Asunto(s)
Reprogramación Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Embrión de Mamíferos/metabolismo , Células Madre Embrionarias/metabolismo , Fibroblastos/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Estrés Mecánico , Animales , Embrión de Mamíferos/citología , Embrión de Mamíferos/efectos de los fármacos , Células Madre Embrionarias/citología , Células Madre Embrionarias/efectos de los fármacos , Femenino , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento , Masculino , Ratones
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