RESUMEN
Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form-AlCl3) at different concentrations (0.1-100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker ß3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.
Asunto(s)
Cloruro de Aluminio/toxicidad , Células Madre Embrionarias/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Madre Embrionarias/patología , Femenino , Masculino , Ratones , Células-Madre Neurales/patología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Fenotipo , Telencéfalo/efectos de los fármacos , Telencéfalo/embriologíaRESUMEN
Human pluripotent stem cells bring promise in regenerative medicine due to their self-renewing ability and the potential to become any cell type in the body. Moreover, pluripotent stem cells can produce specialized cell types that are affected in certain diseases, generating a new way to study cellular and molecular mechanisms involved in the disease pathology under the controlled conditions of a scientific laboratory. Thus, induced pluripotent stem cells (iPSC) are already being used to gain insights into the biological mechanisms of several human disorders. Here we review the use of iPSC as a novel tool for disease modeling in the lab.
Asunto(s)
Modelos Biológicos , Enfermedades del Sistema Nervioso/patología , Células Madre Pluripotentes/patología , Diferenciación Celular , Proliferación Celular , Células Madre Embrionarias/patología , Humanos , FenotipoRESUMEN
Since the derivation of the first human embryonic stem cell (hESC) lines by Thomson and coworkers in 1998, more than 1,200 different hESC lines have been established worldwide. Nevertheless, there is still a recognized interest in the establishment of new lines of hESC, particularly from HLA types and ethnic groups currently underrepresented among the available lines. The methodology of hESC derivation has evolved significantly since 1998, when human LIF (hLIF) was used for maintenance of pluripotency. However, there are a number of different strategies for the several steps involved in establishing a new line of hESC. Here we make a survey of the most relevant parameters used between 1998 and 2010 for the derivation of the 375 hESC lines deposited in two international stem cell registries, and able to form teratomas in immunocompromised mice. Although we identify some trends in the methodology for establishing hESC lines, our data reveal a much greater heterogeneity of strategies than what is used for derivation of murine ESC lines, indicating that optimum conditions have not been consolidated yet, and thus, hESC establishment is still an evolving field of research.