RESUMO
The donation of human embryos for the derivation of embryonic stem cell lines that may be used in the development of therapeutic products raises more complex ethical, practical and regulatory problems than the donation of embryos for non-clinical research. This review considers these issues and offers recommendations for good practice.
Assuntos
Células-Tronco Embrionárias/transplante , Obtenção de Tecidos e Órgãos , Animais , Linhagem Celular , Seleção do Doador/ética , Células-Tronco Embrionárias/citologia , Fertilização in vitro , Humanos , Doadores Vivos/ética , Doadores Vivos/legislação & jurisprudência , Manejo de Espécimes , Pesquisa com Células-Tronco/ética , Pesquisa com Células-Tronco/legislação & jurisprudência , Transplante de Células-Tronco/ética , Transplante de Células-Tronco/normas , Bancos de Tecidos , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/legislação & jurisprudênciaRESUMO
Mesenchymal stem cells (MSCs) derived from young (6 week) and aged (56 week) Wistar rats were cultured at standard (37 degrees C) and reduced (32 degrees C) temperature and compared for age markers and stress levels. (ROS, NO, TBARS, carbonyls, lipofuscin, SOD, GPx, apoptosis, proteasome activity) and heat shock proteins (HSP27, -60, -70, -90). Aged MSCs display many of the stress markers associated with aging in other cell types, but results vary across marker categories and are temperature dependant. In young MSCs, culturing at reduced temperature had a generally beneficial effect: the anti-apoptotic heat shock proteins HSP 27, HSP70, and HSP90 were up-regulated; pro-apoptotic HSP60 was downregulated; SOD, GPx increased; and levels in ROS, NO, TBARS, carbonyl, and lipofuscin were diminished. Apoptosis was reduced, but also proteasome activity. In contrast, in aged MSCs, culturing at reduced temperature generally produced no 'beneficial' changes in these parameters, and can even have detrimental effects. Implications for tissue engineering and for stem cell gerontology are discussed. The results suggest that a 'hormesis' theory of stress response can be extended to MSCs, but that cooling cultivation temperature stress produces positive effects in young cells only.
Assuntos
Senescência Celular , Células-Tronco Mesenquimais/patologia , Células-Tronco Mesenquimais/fisiologia , Temperatura , Envelhecimento , Animais , Apoptose , Feminino , Citometria de Fluxo , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/metabolismo , Homeostase/fisiologia , Lipofuscina/metabolismo , Células-Tronco Mesenquimais/citologia , Óxido Nítrico/metabolismo , Oxirredução , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The role of adult mesenchymal stem cells (MSC) in tissue maintenance and regeneration has received significant attention of late. Questions arise to what extent these cells are either subject to, or causes of aging; whether age-related changes in these cells are due to intrinsic factors or induced by the somatic environment. This review collates and examines recent data in support of these different theories. By means of introduction, a brief overview is given of current MSC definitions and their basic role in tissue regeneration followed by a comparative analysis of gerontological studies involving MSC. Evidence for extrinsic aging and various aging markers relating to morphology, proliferation, signalling, senescence markers, telomeres and telomerase, and other indicators is discussed. We observe that while the literature might often appear to conflict, many apparent discrepancies are attributable to inconsistent methods of extracting and isolating MSC which in fact contains various subsets of adult stem cells, varying not only in their differentiation potential but also in their vulnerability to senescence--ranging from quasi-somatic lifespan to perennial vigour. Thus, mesenchymal stem cells emerge as both subject to and key mediators of organismal aging.
Assuntos
Envelhecimento/fisiologia , Células-Tronco Mesenquimais/fisiologia , Biomarcadores , Proliferação de Células , Humanos , Células-Tronco Mesenquimais/citologia , Transdução de Sinais , Telômero/fisiologiaRESUMO
One of the microglial cell functions is the removal of modified extracellular proteins in the brain. The connection between protein oxidation, proteolysis, and microglial activation is the topic of this review. The effect of various activation agents on microglial cells with regard to changes in substrate uptake, proteolytic capacity and degradation efficiency of different types of oxidized protein materials is reviewed. It is shown that different activation stimuli initiate substrate-specific modulation for uptake and proteolysis, influencing an array of factors including receptor expression, lysosomal pH, and proteasome subunit composition. Age-related alterations in activation and proteolytic capacity in microglial cells are also discussed. In ageing, proteolytic effectiveness is diminished, while microglial cells are chronically activated and lose the oxidative burst ability, possibly supporting a 'vicious circle' of macrophage-induced neurodegeneration.