Response to Letter Regarding Article, “Iron-Oxide Labeling and Outcome of Transplanted Mesenchymal Stem Cells in the Infarcted Myocardium” We appreciate the comments of Drs Sadek and Garry on our study. 1 We agree that ‘the competent immune system of the rat may have recognized the mesenchymal cells as foreign and eliminated those cells via cellular rejection.‘ We also agree that studies with autologous stem cells or delivery of allogeneic stem cells into an immunocompromised host could improve the chance of cell survival and the probability of generating a true positive magnetic resonance imaging signal from the implanted cells. However, we disagree that the design of our study created ‘misleading‘ conclusions. Our study was not designed to confirm or refute the immunoprivileged prop- erties of mesenchymal stem cells. We describe a scenario in which the magnetic resonance image continue to provide a positive signal from the superparamagnetic iron oxide marker despite the disappear- ance of the implanted, labeled cells. We showed that the reason for this finding emerged from the superparamagnetic iron oxide marker that was engulfed by resident macrophages. This may also occur after autologous stem cell transplantation, especially after long-time ex vivo expansion, as the cells may change their phenotype 2 and may be rejected after transplantation. In addition, even autologous cells could die from other causes such as trauma, ischemia, or apoptosis. We believe that our model is suitable to demonstrate a clinically relevant scenario in which the implanted superparamagnetic iron oxide–labeled cells died and the magnetic resonance imaging signal arose from cardiac macrophages that engulfed the superparamagnetic iron oxide nanoparticles. 1 Disclosure None. Yoram Amsalem, MD Micha S. Feinberg, MD Natalie Landa, BSc Liron Miller, MSc Radka Holbova Orna Shaharabani-Yosef, PhD Israel M. Barbash, MD Jonathan Leor, MD Neufeld Cardiac Research Institute Tel-Aviv University Sheba Medical Center Tel-Hashomer, Israel Yael Mardor, PhD Dianne Daniels, MSc Aharon Ocherashvilli, PhD The Advanced Technology Center Sheba Medical Center Tel-Hashomer, Israel References 1. Amsalem Y, Mardor Y, Feinberg MS, Landa N, Miller L, Daniels D, Ocherashvilli A, Holbova R, Yosef O, Barbash IM, Leor J. Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation. 2007;116(suppl I):I-38 –I-45. 2. Zhang CC, Lodish HF. Murine hematopoietic stem cells change their surface phenotype during ex vivo expansion. Blood. 2005;105:4314 – 4320. (Circulation. 2008;117:e307.) © 2008 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.107.760306 e307 Correspondence by guest on May 1, 2016 http://circ.ahajournals.org/ Downloaded from