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Am J Physiol Heart Circ Physiol (June 6, 2008). doi:10.1152/ajpheart.00094.2008 Free Article
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Submitted on January 28, 2008
Revised on May 20, 2008
Accepted on June 3, 2008

Bone marrow-derived stromal cells home to and remain in the infarcted rat heart, but fail to improve function: An in vivo cine-MRI study

Carolyn A Carr1*, Daniel J Stuckey1, Louise Tatton2, Damian J Tyler1, Sarah JM Hale2, Dominic Sweeney2, Jürgen E Schneider3, Enca Martin-Rendon2, George K Radda4, Sian E Harding5, Suzanne M Watt2, and Kieran Clarke1

1 University of Oxford
2 National Blood Service
3 Wellcome Trust Centre for Human Genetics
4 Oxford University
5 Imperial College

* To whom correspondence should be addressed. E-mail: carolyn.carr{at}dpag.ox.ac.uk.

Basic and clinical studies have shown that bone marrow cell therapy can improve cardiac function following infarction. In experimental animals, reported stem cell-mediated changes range from no measurable improvement to the complete restoration of function. In the clinic, however, the average improvement in left ventricular ejection fraction is around 2-3%. A possible explanation for the discrepancy between basic and clinical results is that few basic studies have used the MRI methods that were used in clinical trials for measuring cardiac function. Consequently, we employed cine MR to determine the effect of bone marrow stromal cells (BMSCs) on cardiac function in rats. Cultured rat BMSCs were characterized using flow cytometry and labeled with iron oxide particles and a fluorescent marker to allow in vivo cell tracking and ex vivo cell identification, respectively. Neither label affected in vitro cell proliferation or differentiation. Rat hearts were infarcted and BMSCs or control media were injected into the infarct periphery (n = 34) or infused systemically (n = 30). MRI was used to measure cardiac morphology and function and to determine cell distribution for 10 weeks after infarction and cell therapy. In vivo MRI, histology and cell re-isolation confirmed successful BMSC delivery and retention within the myocardium throughout the experiment. However, no significant improvement in any measure of cardiac function was observed at any time. We conclude that cultured BMSCs are not the optimal cell population to treat the infarcted heart.




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