Tracking cardiac engraftment and distribution of implanted bone marrow cells: Comparing intra-aortic, intravenous, and intramyocardial delivery.
OBJECTIVE
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.
Li
Shu-Hong
SH
Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Lai
Teresa Y Y
TY
Sun
Zhuo
Z
Han
Mihan
M
Moriyama
Eduardo
E
Wilson
Brian
B
Fazel
Shafie
S
Weisel
Richard D
RD
Yau
Terrence
T
Wu
Joseph C
JC
Li
Ren-Ke
RK
D000704:Analysis of Variance; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002465:Cell Movement; D002470:Cell Survival; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D007150:Immunohistochemistry; D007267:Injections / Q000379:methods*; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D049409:Luciferases, Firefly / Q000032:analysis*; D008163:Luminescent Measurements; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000628:therapy; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D049409:Luciferases, Firefly