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RESEARCH PRODUCT
A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells
Xavier NissanAnne-laure JaskowiakAlessandra Lo CiceroAnne-laure EgesipeBenjamin BrinonAnnachiara De Sandre-giovannoliAnnachiara De Sandre-giovannoliLino FerreiraNicolas LévyNicolas LévyJohana TournoisPatrícia R. Pitrezsubject
0301 basic medicineCell typecongenital hereditary and neonatal diseases and abnormalitiesPhenotypic screeningInduced Pluripotent Stem CellsRetinoic acidTretinoinBiologyArticle03 medical and health scienceschemistry.chemical_compoundProgeriaOsteogenesis[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN]medicineHumansInduced pluripotent stem cellChildIsotretinoinGeneticsProgeriaMultidisciplinaryintegumentary systemGuided Tissue RegenerationMesenchymal stem cellnutritional and metabolic diseasesAging PrematureCell DifferentiationMesenchymal Stem Cellsmedicine.diseaseProgerinAlkaline PhosphataseLamin Type A3. Good healthCell biologyHigh-Throughput Screening Assays030104 developmental biologychemistryGene Expression Regulation[ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN]Alkaline phosphatasedescription
AbstractHutchinson-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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-10-01 | Scientific Reports |