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

Ferreira, Lino

Nissan, Xavier

Pitrez, Patricia R.

Rocha, I.

Vazão, Helena

Universidade do Minho: RepositoriUM

46OBJECTIVESTo study the vulnerability of smooth muscle cells (SMCs) in Hutchinson-Gilford Progeria Syndrome (HGPS).WORK PLANHutchinson-Gilford Progeria Syndrome is a rare, progressive premature aging disease in children that leads to vascular SMCs degeneration and premature atherosclerosis.Death occurs at a mean age of 13 years, usually from heart attack or stroke. One of the hallmarks of the disease is the dramatic loss of vascular SMCs in large arteries. In consequence, the arteries undergo vascular remodeling and calcification. So far, it is unclear the reason underlining the sensitivity of SMCs in the context of the disease.To clarify the mechanisms behind SMCs loss, it’s important to have human HGPSSMC; however, these cells are difficult to obtain from Progeria patients. Therefore, we derived HGPS induced pluripotent stem cells (iPSCs) from skin fibroblasts and then differen- tiate them into SMCs.RESULTSIn this work, iPSCs obtained from HGPS fibro-blast patients were successfully differentiated into HGPS-SMCs. These HGPS-SMCs showed impaired maturation and an upregulation of pro-geria markers when comparing with SMCs differ-entiated from healthy iPSCs. HGPS-SMCs shared similar features observed on progerin-express-ing cells such as activation of several effectors of NOTCH signaling pathway and response to farnesyltransferase inhibitors. Therefore we have developed a cell model that is suitable for drug screening and to study the mechanism of SMC loss. This finding opens new opportunities for the treatment of HGPS disease and diseases related to vascular ageing.Vascular cells derived from Hutchinson-Gilford progeria syndrome (HGPS) induciblepluripotent stem cellsPatricia R. PitrezMIT Portugal Bioengineering Systems, Biological Engineering, IBB Institute for Biotechnologyand Bioengineering, Centre of Biological Engineering, University of Minho, Portugalpitrezpatricia@gmail.comBackground:  MSc. in Biological Engineering, University of Minho, PortugalStarting year:  2010Research team:  Helena Vazão1 , Xavier Nissan2Supervisors: Lino Ferreira1, Isabel Rocha3 1CNC - Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal 2CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, Evry cedex, France 3IBB – Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, Braga, Portugal

Vascular cells derived from Hutchinson-Gilford progeria syndrome (HGPS) inducible pluripotent stem cells

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Universidade do Minho: RepositoriUM