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1.
Cell ; 168(3): 473-486.e15, 2017 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-28129541

RESUMO

Interspecies blastocyst complementation enables organ-specific enrichment of xenogenic pluripotent stem cell (PSC) derivatives. Here, we establish a versatile blastocyst complementation platform based on CRISPR-Cas9-mediated zygote genome editing and show enrichment of rat PSC-derivatives in several tissues of gene-edited organogenesis-disabled mice. Besides gaining insights into species evolution, embryogenesis, and human disease, interspecies blastocyst complementation might allow human organ generation in animals whose organ size, anatomy, and physiology are closer to humans. To date, however, whether human PSCs (hPSCs) can contribute to chimera formation in non-rodent species remains unknown. We systematically evaluate the chimeric competency of several types of hPSCs using a more diversified clade of mammals, the ungulates. We find that naïve hPSCs robustly engraft in both pig and cattle pre-implantation blastocysts but show limited contribution to post-implantation pig embryos. Instead, an intermediate hPSC type exhibits higher degree of chimerism and is able to generate differentiated progenies in post-implantation pig embryos.


Assuntos
Quimerismo , Edição de Genes , Mamíferos/embriologia , Animais , Blastocisto , Sistemas CRISPR-Cas , Bovinos , Embrião de Mamíferos/citologia , Feminino , Humanos , Masculino , Mamíferos/classificação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Células-Tronco Pluripotentes , Ratos , Ratos Sprague-Dawley , Sus scrofa
2.
Rev. neurol. (Ed. impr.) ; 63(1): 5-10, 1 jul., 2016. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-154385

RESUMO

Introducción. La enfermedad de Alzheimer (EA) es la primera causa de demencia mundial. Cada vez son más los esfuerzos para lograr una detección temprana del deterioro cognitivo y surgen en el panorama científico entidades diagnósticas como el deterioro cognitivo leve (DCL) y las quejas subjetivas de memoria (QSM). Debido a ello, aparecen numerosos biomarcadores estudiados para conseguir dicho objetivo, entre ellos la tomografía de coherencia óptica. Sujetos y métodos. Se ha realizado un estudio que utiliza la tomografía de coherencia óptica para medir el grosor macular y la capa de fibras nerviosas de la retina en pacientes diagnosticados de EA (n = 36), pacientes con DCL (n = 33), en individuos con QSM (n = 24) y en sujetos control (n = 45). Resultados. Se han encontrado diferencias estadísticamente significativas en cuanto al grosor macular entre todos los grupos estudiados (QSM: 261,8 ± 25,88 μm; DCL: 259,19 ± 22,582 μm; EA leve: 258,53 ± 14,804 μm; EA moderada: 249,32 ± 18,467 μm) y sujetos control (271,96 ± 15,57 μm). Respecto a la capa de fibras nerviosas de la retina, ocurre de igual manera, y la diferencia es estadísticamente significativa frente al grupo control (94,51 ± 9,203 μm) de todos los grupos (QSM: 90,44 ± 9,059 μm; DCL: 89,4 ± 10,421 μm; EA leve: 87,12 ± 10,279 μm; EA moderada: 82,25 ± 10,636 μm). Conclusión. La tomografía de coherencia óptica podría situarse como un futuro biomarcador y una herramienta de apoyo para facilitar el diagnóstico precoz del deterioro cognitivo y de la EA (AU)


Introduction. Alzheimer’s disease (AD) is the leading cause of dementia in the world today. Increasingly greater efforts are being made to be able to detect cognitive impairment in earlier stages, and diagnostic entities such as mild cognitive impairment (MCI) and subjective memory complaints (SMC) are appearing. The number of biomarkers studied with the aim of reaching this goal continues to rise, and include optical coherence tomography. Subjects and methods. The study conducted employed optical coherence tomography to measure the macular thickness and the retinal nerve fibre layer in patients diagnosed with AD (n = 36), in patients with MCI (n = 33), in individuals with SMC (n = 24) and in control subjects (n = 45). Results. Statistically significant differences have been found in terms of the macular thickness among all the groups studied (SMC: 261.8 ± 25.88 μm; MCI: 259.19 ± 22.582 μm; mild AD: 258.53 ± 14.804 μm; moderate AD: 249.32 ± 18.467 μm) and control subjects (271.96 ± 15.57 μm). The same occurs as regards the retinal nerve fibre layer and the difference is statistically significant compared with the control group (94.51 ± 9.203 μm) of all the groups (SMC: 90.44 ± 9.059 μm; MCI: 89.4 ± 10.421 μm; mild AD: 87.12 ± 10.279 μm; moderate AD: 82.25 ± 10.636 μm). Conclusion. Optical coherence tomography could be a future biomarker and support tool to facilitate the early diagnosis of cognitive impairment and AD (AU)


Assuntos
Humanos , Tomografia de Coerência Óptica/métodos , Demência/diagnóstico , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Degeneração Macular/diagnóstico , Biomarcadores/análise , Estudos de Casos e Controles , Transtornos da Memória/diagnóstico , Envelhecimento
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