Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials.
BACKGROUND
Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model.


RESULTS
Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques.


CONCLUSIONS
The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.
Hou
Dongming
D
Indiana University School of Medicine, Indianapolis, IN, USA.
Youssef
Eyas Al-Shaykh
EA
Brinton
Todd J
TJ
Zhang
Ping
P
Rogers
Pamela
P
Price
Erik T
ET
Yeung
Alan C
AC
Johnstone
Brian H
BH
Yock
Paul G
PG
March
Keith L
KL
D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D002986:Clinical Trials as Topic / Q000379:methods; D003331:Coronary Vessels; D005260:Female; D006085:Graft Survival; D006801:Humans; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007668:Kidney / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000601:surgery; D009206:Myocardium / Q000473:pathology; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D015125:Oxyquinoline / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011897:Random Allocation; D015203:Reproducibility of Results; D012107:Research Design; D013154:Spleen / Q000473:pathology; D034421:Sus scrofa; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C032950:indium oxine; D015125:Oxyquinoline