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European Journal of Heart Failure 2006 8(6):555-563; doi:10.1016/j.ejheart.2005.11.006
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© 2005 European Society of Cardiology

Effect of aging on the pluripotential capacity of human CD105+ mesenchymal stem cells

Santiago Rouraa, Jordi Farréb, Carolina Soler-Botijaa, Anna Llacha, Leif Hove-Madsena, Jordi J. Cairób, Francesc Gòdiab, Juan Cincaa and Antoni Bayes-Genisa,*

a Laboratory of Cell Physiology, Cardiology Service, Hospital de la Santa Creu i Sant Pau, ICCC, Universitat Autònoma de Barcelona Barcelona, Spain
b Departament d'Enginyeria Química, Escola Tècnica Superior d'Enginyeria, E.T.S.E., Universitat Autònoma de Barcelona Barcelona, Spain

* Corresponding author. Cardiac Regeneration Program, Cardiology Service- ICCC, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain. Tel.: +34 93 5565765. E-mail address: abayesgenis{at}hsp.santpau.es


   Abstract

Background: Whether aging modifies mesenchymal stem cell (MSC) properties is unknown.

Aim: To compare the differentiation capacity of human CD105+ MSCs obtained from young and elderly donors.

Methods and results: Cells were obtained from young (n = 10, 24 ± 6.4 years) and elderly (n = 9, 77 ± 8.4 years) donors. Cell senescence was assessed by telomere length assays and lipofuscin accumulation. Cell pluripotentiality was analysed by adipogenic and osteogenic induction media, and myocyte phenotype was attempted with 5-azacytidine (5-AZ). Immunofluorescence, Western blot, transmission electron microscopy and fluo-4 confocal imaging were used to analyse the sarcomere, gap junctions and Ca2+ dynamics. Cells obtained from young and elderly donors showed no significant differences in relative telomere length (40.1 ± 6.4% and 40.3 ± 3.6%, p = 0.9) and lipofuscin accumulation. Adipogenic and osteogenic potential of CD105+ MSCs was demonstrated. 5-AZ induced increased expression of sarcomeric proteins without complete sarcomere organization. Treated cells also showed increased presence of connexin-43 both in young and old donor-derived cells. Intercellular communications were verified by the observation of gap junctions and passage of Ca2+ between neighbouring cells. Spontaneous Ca2+ raises did not significantly increase after 5-AZ treatment in both age groups.

Conclusion: Age does not influence the adipogenic and myogenic differentiation potential of human CD105+ MSCs.

Key Words: Cardiomyogenic differentiation • Stem cells • Age • Senescence

Received November 23, 2004; Revised July 25, 2005; Accepted November 15, 2005


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