European Heart Journal Advance Access originally published online on March 1, 2006
European Heart Journal 2006 27(9):1114-1122; doi:10.1093/eurheartj/ehi818
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A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction
1 Boston Scientific Corporation, Natick, MA USA
2 Cardiovascular Division, Hospital of the University of Pennsylvania, University of Pennsylvania Medical Center, 3400 Spruce Street, 9 Gates, Philadelphia, PA 19104, USA
Received 12 December 2005; revised 31 January 2006; accepted 9 February 2006; online publish-ahead-of-print 1 March 2006.
* Corresponding author. Tel: +1 215 615 3060; fax: +1 215 615 3073. E-mail address: robert.wilensky{at}uphs.upenn.edu
Aims Mesenchymal stem cells (MSCs), rare bone marrow-derived stem cell precursors of non-haematopoietic tissues, have shown promise in potentially repairing infarcted myocardium. These and similar cell types are being tested clinically, but understanding of delivery and subsequent biodistribution is lacking. This study was designed to quantitatively compare MSC engraftment rates after intravenous (IV), intracoronary (IC), or endocardial (EC) delivery in a porcine myocardial infarction (MI) model.
Methods and results Allogeneic, male MSCs were cultured from porcine bone marrow aspirates. Iridium nanoparticles were added during culturing and internalized by the MSCs. An MI was induced in female swine (27–40 kg in size) by prolonged balloon occlusion of the mid-left anterior descending artery. Animals (n=6 per group) were randomized to one of three delivery methods. Cellular engraftment was determined 14±3 days post-delivery by measuring ex-vivo the iridium nanoparticle concentration in the infarct. Confirmation of cellular engraftment utilized both DiI and fluorescence in situ hybridization (FISH) labelling techniques. During MSC infusion, no adverse events were noted. However, following IC infusion, half of the pigs exhibited decreased blood flow distal to the infusion site. At 14 days, the mean number of engrafted cells within the infarct zone was significantly greater (P
0.01) following IC infusion than either EC injection or IV infusion and EC engraftment was greater than IV engraftment (P0.01). There was less systemic delivery to the lungs following [EC vs. IV (P=0.02), EC vs. IC (P=0.06)]. Both DiI and FISH labelling demonstrated the presence of engrafted male MSCs within the female infarcted tissue.
Conclusion IC and EC injection of MSCs post-MI resulted in increased engraftment within infarcted tissue when compared with IV infusion, and IC was more efficient than EC. However, IC delivery was also associated with a higher incidence of decreased coronary blood flow. EC delivery into acutely infarcted myocardial tissue was safe and well tolerated and was associated with decreased remote organ engraftment with compared with IC and IV deliveries.
Key Words: Intracoronary • Intravenous • Endocardial • Bone marrow derived stem cell • Regeneration
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