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1.
Semin Liver Dis ; 42(4): 423-433, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36044928

RESUMEN

Despite the rising prevalence of nonalcoholic fatty liver disease (NAFLD), the underlying disease pathophysiology remains unclear. There is a great need for an efficient and reliable "human" in vitro model to study NAFLD and the progression to nonalcoholic steatohepatitis (NASH), which will soon become the leading indication for liver transplantation. Here, we review the recent developments in the use of three-dimensional (3D) liver organoids as a model to study NAFLD and NASH pathophysiology and possible treatments. Various techniques that are currently used to make liver organoids are discussed, such as the use of induced pluripotent stem cells versus primary cell lines and human versus murine cells. Moreover, methods for inducing lipid droplet accumulation and fibrosis to model NAFLD are explored. Finally, the limitations specific to the 3D organoid model for NAFLD/NASH are reviewed, highlighting the need for further development of multilineage models to include hepatic nonparenchymal cells and immune cells. The ultimate goal is to be able to accurately recapitulate the complex liver microenvironment in which NAFLD develops and progresses to NASH.


Asunto(s)
Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Organoides/metabolismo , Progresión de la Enfermedad , Hígado/metabolismo , Microambiente Tumoral
3.
Clin Transl Sci ; 11(2): 166-174, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29271559

RESUMEN

Drug discovery and development is commonly schematized as a "pipeline," and, although appreciated by drug developers to be a useful oversimplification, this cartology may perpetuate inaccurate notions of straightforwardness and is of minimal utility for process engineering to improve efficiency. To create a more granular schema, a group of drug developers, researchers, patient advocates, and regulators developed a crowdsourced atlas of the steps involved in translating basic discoveries into health interventions, annotated with the steps that are particularly prone to difficulty or failure. This Drug Discovery, Development, and Deployment Map (4DM), provides a network view of the process, which will be useful for communication and education to those new to the field, orientation and navigation of individual projects, and prioritization of technology development and re-engineering endeavors to improve efficiency and effectiveness. The 4DM is freely available for utilization, modification, and further development by stakeholders across the translational ecosystem.


Asunto(s)
Desarrollo de Medicamentos/métodos , Descubrimiento de Drogas/métodos , Colaboración Intersectorial , Proyectos de Investigación , Investigación Biomédica Traslacional/métodos , Tecnología Biomédica/métodos , Ensayos Clínicos como Asunto , Comunicación , Humanos , Aprendizaje , Miositis Osificante/tratamiento farmacológico , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Neuropéptido Y/antagonistas & inhibidores , Neuropéptido Y/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Estados Unidos , United States Food and Drug Administration
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