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Title: A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells
Authors: Lo Cicero, Alessandra
Jaskowiak, Anne-Laure
Egesipe, Anne-Laure
Tournois, Johana
Brinon, Benjamin
Pitrez, Patrícia R. 
Ferreira, Lino
de Sandre-Giovannoli, Annachiara
Lévy, Nicolas 
Nissan, Xavier
Issue Date: 14-Oct-2016
Publisher: Springer Nature
Project: Institut National de la Santé et de la Recherche Médicale (INSERM), the National infrastructure Engineering for Pluripotent and differentiated Stem cells (INGESTEM), The region Ile-De-France (DIM Biothérapies), Evry Val d’Essonne University (UEVE), Association Française contre les Myopathies (AFM) and Genopole 
Serial title, monograph or event: Scientific Reports
Volume: 6
Issue: 1
Abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders.
ISSN: 2045-2322
DOI: 10.1038/srep34798
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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