ABSTRACT
In vitro modeling of neurodegenerative diseases is now possible by using patient-derived induced pluripotent stem cells (iPS). Through them, it is nowadays conceivable to obtain human neurons and glia, and study diseases cellular and molecular mechanisms, an attribute that was previously unavailable to any human condition. Amyotrophic lateral sclerosis (ALS) is one of the diseases that has gained a rapid advance with iPS technology. By differentiating motor neurons from iPS cells of ALS- patients, we are studying the mechanisms underlying ALS- disease onset and progression. Here, we introduce a cellular platform to help maintain longevity of ALS iPS-motor neurons, a cellular feature relevant for most late-onset human diseases. Long term cultures of patient-derived iPS cells might prove to be critical for the development of personalized-drugs.
Actualmente es posible modelar in vitro enfermedades neurodegenerativas humanas mediante el uso de células madre pluripotentes inducidas (iPS) derivadas del paciente. A través de ellas, es hoy concebible obtener neuronas y glía humanas, y estudiar mecanismos celulares y moleculares de enfermedades, un atributo que anteriormente no era posible para ninguna condición humana. La esclerosis lateral amiotrófica (ELA) es una de las enfermedades que se ha beneficiado con la tecnología de iPS. Al diferenciar neuronas motoras de células iPS obtenidas de pacientes con ELA, hemos iniciado estudios sobre los mecanismos que subyacen a la aparición y progresión de la enfermedad. Aquí, presentamos el desarrollo de una plataforma celular que permite extender la longevidad de las neuronas motoras derivadas de iPS, una característica relevante para la mayoría de las enfermedades humanas de inicio tardío. Los cultivos a largo plazo de células iPS provenientes de pacientes pueden ser determinantes en el desarrollo de terapias asociadas a la medicina de precisión.
Subject(s)
Humans , Animals , Mice , Induced Pluripotent Stem Cells/cytology , Amyotrophic Lateral Sclerosis/metabolism , Immunohistochemistry , Cell Line , Coculture Techniques , Amyotrophic Lateral Sclerosis/pathology , Amyotrophic Lateral Sclerosis/therapyABSTRACT
BACKGROUND: Little is known about the associations between symptoms of asthma, pulmonary function tests, and atopy in developing countries. While asthma in children is often associated with atopy, some studies of wheezing illness have found little or no association, leading to suggestions that there are subgroups of wheezing illness. The ISAAC study recently reported that the prevalence of reported asthma symptoms in Lima, Peru was among the highest in the world, but did not report on the atopic status of the subjects. METHODS: A cross sectional survey was conducted of children aged 8-10 years who had previously participated in a cohort study of respiratory and diarrhoeal illnesses in infancy. Questionnaires were administered asking about respiratory symptoms and asthma diagnoses, pulmonary function tests were performed before and after exercise on a treadmill, and atopy was determined from skin prick tests and specific serum IgE levels. RESULTS: A total of 793 children participated in the survey. The prevalence of asthma related symptoms in the last 12 months was 23.2%, but only 3.8% of children reported a recent asthma attack. The mean differences in pretest percentage predicted forced expiratory volume in one second (FEV(1)) were 8.1% (95% CI 2.4 to 13.8) between children who did and did not report an asthma attack in the last 12 months, and 5.3% (95% CI 2.8 to 7.9) in children who did and did not report respiratory symptoms. The corresponding differences in mean percentage fall in FEV(1) after exercise were 3.1% (95% CI -1 to 7.1) and 5.1% (95% CI 3.4 to 6.8). Recent asthma or respiratory symptoms were not associated with atopy in this population (odds ratios 1.29 (95% CI 0.56 to 2.97) and 0.91 (95% CI 0.61 to 1.37), respectively). CONCLUSIONS: Most asthma in these children was unrecognised and mild. Asthma and asthma symptoms in this population do not seem to be related to atopy.
