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Cellular reprogramming as a tool to model human aging in a dish

Pitrez, Patrícia R.; Monteiro, Luís M.; Borgogno, Oliver; Nissan, Xavier; Mertens, Jerome; Ferreira, Lino

The design of human model systems is highly relevant to unveil the underlying mechanisms of aging and to provide insights on potential interventions to extend human health and life span. In this perspective, we explore the potential of 2D or 3D culture models comprising human induced pluripotent stem cells and transdifferentiated cells obtained from aged or age-related disorder-affected donors to enhance our un...


Ghrelin delays premature aging in Hutchinson-Gilford progeria syndrome

Ferreira-Marques, Marisa; Carvalho, André; Franco, Ana Catarina; Leal, Ana; Botelho, Mariana; Carmo-Silva, Sara; Águas, Rodolfo; Cortes, Luísa

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition that arises from a single nucleotide alteration in the LMNA gene, leading to the production of a defective lamin A protein known as progerin. The accumulation of progerin accelerates the onset of a dramatic premature aging phenotype in children with HGPS, characterized by low body weight, lipodystrophy, metabolic dysfunction, skin...


Induced pluripotent stem cell-derived vascular networks to screen nano-bio inte...

Estronca, Luís; Francisco, Vitor; Pitrez, Patrícia; Honório, Inês; Carvalho, Lara; Vazão, Helena; Blersh, Josephine; Rai, Akhilesh; Nissan, Xavier

This work was funded by FEDER through the Program COMPETE and by Portuguese fund through FCT in context of the projects PTDC/SAU-TOX/121887/2010, POCI-01-0145-FEDER-029229, POCI-01-0145-FEDER-016390 and POCI-01-0145-FEDER-029414, as well as the European project ERAatUC (ref. 669088). PRP wishes to thank FCT for a BD fellowship (SFRH/BD/71042/2010). The iMM Fish Facility was supported by CONGENTO LISBOA-01-0145-...


Induced pluripotent stem cell-derived vascular networks to screen nano-bio inte...

Estronca, Luís; Francisco, Vitor; Pitrez, Patrícia; Honório, Inês; Carvalho, Lara; Vazão, Helena; Blersch, Josephine; Rai, Akhilesh; Nissan, Xavier

The vascular bioactivity/safety of nanomaterials is typically evaluated by animal testing, which is of low throughput and does not account for biological differences between animals and humans such as ageing, metabolism and disease profiles. The development of personalized human in vitro platforms to evaluate the interaction of nanomaterials with the vascular system would be important for both therapeutic and r...


Vulnerability of progeroid smooth muscle cells to biomechanical forces is media...

Pitrez, Patrícia R.; Estronca, Luís Miguel Beicinha Branco; Monteiro, Luís Miguel Marques; Colell, Guillem; Vazão, Helena

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow...


Vulnerability of progeroid smooth muscle cells to biomechanical forces is media...

Pitrez, Patricia R.; Estronca, Luís; Monteiro, Luís Miguel; Colell, Guillem; Vazão, Helena; Santinha, Deolinda; Harhouri, Karim; Thornton, Daniel

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow...


Substrate Topography Modulates Cell Aging on a Progeria Cell Model

Pitrez, Patrícia R.; Estronca, Luís Miguel Beicinha Branco; Vazão, Helena; Egesipe, Anne-Laure; Le Corf, Amélie; Navarro, Claire; Lévy, Nicolas

Aging is characterized by a progressive accumulation of cellular damage, which leads to impaired function. Little is known whether substrates can influence cell aging. This is of utmost importance in the development of medical devices that are in contact with human tissue for long periods of time. To address this question, we have used an accelerated aging cell model derived from Hutchinson-Gilford Progeria Syn...


A High Throughput Phenotypic Screening reveals compounds that counteract premat...

Lo Cicero, Alessandra; Jaskowiak, Anne-Laure; Egesipe, Anne-Laure; Tournois, Johana; Brinon, Benjamin; Pitrez, Patrícia R.; Ferreira, Lino

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-th...


Vascular cells derived from Hutchinson-Gilford progeria syndrome (HGPS) inducib...

Pitrez, Patricia R.; Vazão, Helena; Nissan, Xavier; Ferreira, Lino; Rocha, I.

To study the vulnerability of smooth muscle cells (SMCs) in Hutchinson-Gilford Progeria Syndrome (HGPS).


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