Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.
Cell Rep
; 9(3): 810-21, 2014 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-25437537
ABSTRACT
Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Avaliação Pré-Clínica de Medicamentos
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Células-Tronco Pluripotentes Induzidas
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Cardiomiopatias Diabéticas
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Modelos Biológicos
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article