RESUMEN
We developed a microfluidic gradient device to utilize as a drug screening system with human induced pluripotent stem cell (hiPSC)-derived motoneurons. The microfluidic channel was asymmetrically designed to generate the concentration gradients and a micropillar array was used to trap and culture the motoneuron spheroids containing motoneurons for 9 days. We optimized the concentration gradients in the microfluidic device using a computational fluid dynamics (CFD) model. We also observed that the motoneuron spheroid-derived neurite network was generated in response to the concentration gradients of riluzole in the microfluidic device. Therefore, this microfluidic gradient device could be useful for screening of various drugs for neurological disease applications.
Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Dispositivos Laboratorio en un Chip , Microfluídica/métodos , Neuronas Motoras/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Riluzol/farmacología , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular , Diseño de Equipo , Humanos , Células Madre Pluripotentes Inducidas/citología , Microfluídica/instrumentación , Neuronas Motoras/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismoRESUMEN
Epicutaneously administered chemical antigens like 2,4-dinitrofluorobenzene (DNFB), evoke an atopic dermatitis (AD)-like dermatitis reaction in NC/Nga mice under specific pathogen free (SPF) conditions. Astragalus membranaceus (AM), is a popular herbal medicine used to treat allergic diseases in East Asia. In the present study, we examined whether AM suppress AD-like skin lesions in NC/Nga mice treated with DNFB under SPF conditions. Oral administration of AM to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. Moreover, IFN-gamma production by CD4(+) T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by AM treatment, although levels of IL-4 and total IgE in serum were not. Study findings suggest that AM may suppress the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IFN-gamma production.