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European Heart Journal Advance Access published online on July 24, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl154
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European Heart Journal © The European Society of Cardiology 2006; all rights reserved
Received February 28, 2006
Revised June 8, 2006
Accepted June 29, 2006

Clinical research

Prostacyclin improves transcoronary myocardial delivery of adipose tissue-derived stromal cells

Rosalinda Madonna 1, Lucia Rinaldi 2, Cosmo Rossi 2, Yong-Jian Geng 3, and Raffaele De Caterina 4 *

1 Institute and Postgraduate School of Cardiology, G. d'Annunzio University--Chieti--Ospedale San Camillo de Lellis, Via C. Forlanini, 50, 66100 Chieti, Italy; University of Texas Health Science Center at Houston and Texas Heart Institute, Houston, TX, USA
2 Institute and Postgraduate School of Cardiology, G. d'Annunzio University--Chieti--Ospedale San Camillo de Lellis, Via C. Forlanini, 50, 66100 Chieti, Italy
3 University of Texas Health Science Center at Houston and Texas Heart Institute, Houston, TX, USA
4 Institute and Postgraduate School of Cardiology, G. d'Annunzio University--Chieti--Ospedale San Camillo de Lellis, Via C. Forlanini, 50, 66100 Chieti, Italy; CNR Institute of Clinical Physiology, Pisa, Italy

* To whom correspondence should be addressed.
Raffaele De Caterina, E-mail: rdecater{at}unich.it


  Abstract

Aims Heart transplantation of adipose tissue-derived stromal cells (ADSCs) is under evaluation as a therapy for cardiac repair. Prostacyclin (PGI2), a vasodilator with additional effects on platelet aggregation and blood cell adhesion, exerts cardioprotection and might favour the myocardial delivery of ADSCs. We investigated the engraftment and influence on cardiac function of the transcoronary delivery of ADSCs and the effects of PGI2 compared with nitroglycerin (NTG) and adenosine (Ado) in isolated-perfused mouse hearts.

Methods and results Infusion of ADSCs at <1 x 106 cells/mL caused no significant changes in contractility and rhythm, whereas higher cell doses caused cardiac dysfunction. Perfusion with PGI2, NTG, and Ado concentration-dependently increased coronary flow (CF). Perfusion with PGI2, at variance from NTG and Ado, increased ADSC delivery and entrance into the myocardial interstitium without affecting ventricular or metabolic functions and CF (engrafted ADSCs, as percentage of control, at doses producing 50% of maximum vasodilation: PGI2: 220 ± 12, P < 0.001; NTG: 110 ± 8, P = N.S.; Ado: 80 ± 5, P = N.S.).

Conclusion PGI2 safely increases myocardial delivery of ADSCs, by mechanisms independent of its vasodilatory properties, with a potential for its use in cell therapy for cardiac repair.

Keywords: Adipose tissue; Stem cells; Cell therapy; Prostacyclin; Cardiac repair; Coronary vasodilators.
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