Cell distribution after intracoronary bone marrow stem cell delivery in damaged and undamaged myocardium: implications for clinical trials.
BACKGROUND
Early randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs. This study was designed to quantify and compare whole body and heart cell distribution after intracoronary or peripheral intravenous injection of autologous bone marrow mononuclear cells in a porcine acute myocardial infarction model with late reperfusion.


METHODS
Myocardial infarction was induced using balloon inflation in the left coronary artery in domestic pigs. At seven days post-myocardial infarction, 1 x 10(8) autologous bone marrow mononuclear cells were labeled with fluorescent marker and/or 99mTc radiotracer, and delivered using intracoronary or peripheral intravenous injection (leg vein).


RESULTS
Scintigraphic analyses and Upsilon-emission radioactivity counting of harvested organs showed a significant cell fraction retained within the heart after intracoronary injection (6 +/- 1.7% of injected radioactivity at 24 hours), whereas following peripheral intravenous cell injection, no cardiac homing was observed at 24 hours and cells were mainly detected within the lungs. Importantly, no difference was observed in the percentage of retained cells within the myocardium in the presence or absence of myocardial infarction. Histological evaluation did not show arterial occlusion in both animal groups and confirmed the presence of bone marrow mononuclear cells within the injected myocardium area.


CONCLUSIONS
Intravenous bone marrow mononuclear cell injection was ineffective to target myocardium. Myocardial cell distribution following intracoronary injection did not depend on myocardial infarction presence, a factor that could be useful for cardiac cell therapy in patients with chronic heart failure of non-ischemic origin or with ischemic myocardium without myocardial infarction.
Forest
Virginie F
VF
INSERM UMR915, l'institut du thorax, IRT-Université de Nantes, 8 quai Moncousu, BP 70721, Nantes, F-44007 Cedex 1, France. virginie.forest@univ-nantes.fr
Tirouvanziam
Ashok M
AM
Perigaud
Christian
C
Fernandes
Sarah
S
Fusellier
Marion S
MS
Desfontis
Jean-Claude
JC
Toquet
Claire S
CS
Heymann
Marie-Françoise M
MF
Crochet
Dominique P
DP
Lemarchand
Patricia F
PF
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002465:Cell Movement; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D009000:Monocytes / Q000637:transplantation*; D009203:Myocardial Infarction / Q000139:chemically induced / Q000628:therapy*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D013552:Swine; D013667:Technetium
D013667:Technetium