TY - JOUR
T1 - Tracking cardiac engraftment and distribution of implanted bone marrow cells
T2 - Comparing intra-aortic, intravenous, and intramyocardial delivery
AU - Li, Shu Hong
AU - Lai, Teresa Y.Y.
AU - Sun, Zhuo
AU - Han, Mihan
AU - Moriyama, Eduardo
AU - Wilson, Brian
AU - Fazel, Shafie
AU - Weisel, Richard D.
AU - Yau, Terrence
AU - Wu, Joseph C.
AU - Li, Ren Ke
N1 - Funding Information:
This research was funded primarily by a grant from the Heart and Stoke Foundation of Ontario (T6069) to R-KL and in part by grants from the Canadian Institutes of Health Research (CIHR; MOP14795) to R-KL and from the CIHR (RMF82498). R-KL is a Career Investigator of the Heart and Stroke Foundation of Canada and holds a Canada Research Chair in cardiac regeneration. The bioluminescence system was supported by the Canadian Foundation for Innovation.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jtcvs.2008.11.001
DO - 10.1016/j.jtcvs.2008.11.001
M3 - Article
C2 - 19379996
AN - SCOPUS:64649102368
SN - 0022-5223
VL - 137
SP - 1225-1233.e1
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 5
ER -