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1.
Proteomes ; 2(1): 53-71, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28250369

RESUMO

Mesenchymal stem cells (MSCs) are undifferentiated cells with an unlimited capacity for self-renewal and able to differentiate towards specific lineages under appropriate conditions. MSCs are, a priori, a good target for cell therapy and clinical trials as an alternative to embryonic stem cells, avoiding ethical problems and the chance for malignant transformation in the host. However, regarding MSCs, several biological implications must be solved before their application in cell therapy, such as safe ex vivo expansion and manipulation to obtain an extensive cell quantity amplification number for use in the host without risk accumulation of genetic and epigenetic abnormalities. Cell surface markers for direct characterization of MSCs remain unknown, and the precise molecular mechanisms whereby growth factors stimulate their differentiation are still missing. In the last decade, quantitative proteomics has emerged as a promising set of techniques to address these questions, the answers to which will determine whether MSCs retain their potential for use in cell therapy. Proteomics provides tools to globally analyze cellular activity at the protein level. This proteomic profiling allows the elucidation of connections between broad cellular pathways and molecules that were previously impossible to determine using only traditional biochemical analysis. However; thus far, the results obtained must be orthogonally validated with other approaches. This review will focus on how these techniques have been applied in the evaluation of MSCs for their future applications in safe therapies.

2.
J Clin Invest ; 111(7): 1073-82, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12671057

RESUMO

Epidemiological studies from both iodine-sufficient and -deficient human populations strongly suggest that early maternal hypothyroxinemia (i.e., low circulating free thyroxine before onset of fetal thyroid function at midgestation) increases the risk of neurodevelopmental deficits of the fetus, whether or not the mother is clinically hypothyroid. Rat dams on a low iodine intake are hypothyroxinemic without being clinically hypothyroid because, as occurs in pregnant women, their circulating 3,5,3'-triiodothyronine level is usually normal. We studied cell migration and cytoarchitecture in the somatosensory cortex and hippocampus of the 40-day-old progeny of the iodine-deficient dams and found a significant proportion of cells at locations that were aberrant or inappropriate with respect to their birth date. Most of these cells were neurons, as assessed by single- and double-label immunostaining. The cytoarchitecture of the somatosensory cortex and hippocampus was also affected, layering was blurred, and, in the cortex, normal barrels were not formed. We believe that this is the first direct evidence of an alteration in fetal brain histogenesis and cytoarchitecture that could only be related to early maternal hypothyroxinemia. This condition may be 150-200 times more common than congenital hypothyroidism and ought to be prevented both by mass screening of free thyroxine in early pregnancy and by early iodine supplementation to avoid iodine deficiency, however mild.


Assuntos
Encéfalo/embriologia , Córtex Cerebral/patologia , Hipotireoidismo/metabolismo , Troca Materno-Fetal , Complicações na Gravidez/sangue , Hormônios Tireóideos/metabolismo , Tiroxina/sangue , Tiroxina/metabolismo , Animais , Peso Corporal , Encéfalo/metabolismo , Movimento Celular , Córtex Cerebral/metabolismo , Feminino , Doenças Fetais/sangue , Doenças Fetais/etiologia , Hipocampo/embriologia , Hipocampo/metabolismo , Hipotireoidismo/etiologia , Imuno-Histoquímica , Iodo/deficiência , Iodo/farmacologia , Neurônios/metabolismo , Gravidez , Ratos , Ratos Wistar , Glândula Tireoide/embriologia , Glândula Tireoide/metabolismo , Tiroxina/fisiologia , Fatores de Tempo
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