Stem Cells
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First published online May 22, 2008
Stem Cells Vol. 26 No. 8 August 2008, pp. 2093 -2103
doi:10.1634/stemcells.2008-0061; www.StemCells.com
© 2008 AlphaMed Press

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TISSUE-SPECIFIC STEM CELLS

Criticality of the Biological and Physical Stimuli Array Inducing Resident Cardiac Stem Cell Determination

Giancarlo Fortea,b, Felicia Carotenutoa, Francesca Pagliaria, Stefania Pagliaric, Paolo Cossaa, Roberta Fiaccaventoa, Arti Ahluwaliad, Giovanni Vozzid, Bruna Vincid, Annalucia Serafinoe, Antonio Rinaldif,g, Enrico Traversaf,g, Luciana Carosellah, Marilena Minieria,g, Paolo Di Nardoa,g

aLaboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Roma, Italy;
bIstituto Nazionale per le Ricerche Cardiovascolari (INRC), Bologna, Italy;
cSyntech srl, Roma, Italy;
dCentro Interdipartimentale di Ricerca "E. Piaggio," Università di Pisa, Pisa, Italy;
eIstituto di Neurobiologia e Medicina Molecolare, Consiglio Nazionale delle Ricerche, Roma, Italy;
fDipartimento di Scienze e Tecnologie Chimiche, Università di Roma Tor Vergata, Roma, Italy;
gCentro per le Nanoscienze, le Nanotecnologie e la Strumentazione Innovativa (NAST), Università di Roma Tor Vergata, Roma, Italy;
hIstituto di Medicina Interna e Geriatria, Università Cattolica S. Cuore, Roma, Italy

Key Words. Mesenchymal stem cells • Cardiac progenitor cells • Three-dimensional scaffolds • Tissue engineering

Correspondence: Correspondence: Paolo Di Nardo, M.D., Laboratorio di Cardiologia Molecolare e Cellulare, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Via Montpellier, 1, 00133 Roma, Italy. Telephone: +39-06-72594215; Fax: +39-06-2024130 or +39-06-72594263; e-mail: dinardo{at}med.uniroma2.it

Received on January 18, 2008; accepted for publication on May 15, 2008.

First published online in STEM CELLS EXPRESS  May 22, 2008.


The replacement of injured cardiac contractile cells with stem cell-derived functionally efficient cardiomyocytes has been envisaged as the resolutive treatment for degenerative heart diseases. Nevertheless, many technical issues concerning the optimal procedures to differentiate and engraft stem cells remain to be answered before heart cell therapy could be routinely used in clinical practice. So far, most studies have been focused on evaluating the differentiative potential of different growth factors without considering that only the synergistic cooperation of biochemical, topographic, chemical, and physical factors could induce stem cells to adopt the desired phenotype. The present study demonstrates that the differentiation of cardiac progenitor cells to cardiomyocytes does not occur when cells are challenged with soluble growth factors alone, but requires strictly controlled procedures for the isolation of a progenitor cell population and the artifactual recreation of a microenvironment critically featured by a fine-tuned combination of specific biological and physical factors. Indeed, the scaffold geometry and stiffness are crucial in enhancing growth factor differentiative effects on progenitor cells. The exploitation of this concept could be essential in setting up suitable procedures to fabricate functionally efficient engineered tissues.

Disclosure of potential conflicts of interest is found at the end of this article.







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