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J Thorac Cardiovasc Surg 2009;137:1225-1233
© 2009 The American Association for Thoracic Surgery

Cardiopulmonary Support

Tracking cardiac engraftment and distribution of implanted bone marrow cells: Comparing intra-aortic, intravenous, and intramyocardial delivery

^a Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada
^b Division of Biophysics and Bioimaging, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada
^c Department of Medicine and Radiology, Stanford University School of Medicine, Stanford, Calif

Received for publication August 14, 2008; revisions received September 29, 2008; accepted for publication November 2, 2008.

^_* Address for reprints: Ren-Ke Li, MD, PhD, MaRS Centre, Toronto Medical Discovery Tower, Room #3-702, 101 College St, Toronto, Ontario, Canada M5G 1L7. (Email: renkeli{at}uhnres.utoronto.ca).

Objectives: Cell therapy improved cardiac function after a myocardial infarction in several preclinical studies; however, the functional benefits were limited in the initial clinical trials, perhaps because of inadequate cell engraftment. We used noninvasive molecular imaging to compare the distribution and myocardial retention of cells implanted by using clinical delivery routes.

Methods: Bone marrow stromal cells isolated from male rats and transfected with a firefly luciferase reporter gene were injected by using 3 increasingly invasive techniques (ie, intravenous, intra-aortic, and intramyocardial) into female rats 3 or 28 days after coronary ligation. Whole-body bioluminescence imaging was performed 2, 24, and 48 hours later; implanted cells were quantified at 48 hours in explanted organs by means of bioluminescence and real-time polymerase chain reaction.

Results: Variations in cell distribution among groups were profound, with nearly complete trapping of the injected cells in the lungs after intravenous delivery. Cell delivery into the aortic root (with the distal aorta occluded) produced minimal cell retention in the heart. Direct intramyocardial injection facilitated the best early targeting of the cells (P < .05 vs intravenous and intra-aortic injection). Rapid signal loss over 48 hours indicated very poor cell survival in all 3 groups, although implanted cell retention was greater in mature compared with acute infarcts.

Conclusions: This is the first study to correlate live cell imaging with quantitative genetic and histologic techniques. Noninvasive molecular imaging tracked delivered cells and will permit the evaluation of new and improved delivery platforms designed to increase cell homing, retention, and engraftment.

This article has been cited by other articles:

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