Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction.
OBJECTIVE
In a blinded, placebo-controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from granulocyte colony-stimulating factor (G-CSF)-mobilized apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large myocardial infarction (MI).


RESULTS
Four days after left anterior descending (LAD) occlusion and reperfusion, cells from BM or apheresis product of saline- (placebo) or G-CSF-injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by magnetic resonance imaging (MRI) of 35.3 +/- 8.5%, no difference between the placebo, G-CSF, and BM groups (P = 0.16 by ANOVA). At 6 weeks, EF fell to a similar degree in the placebo, G-CSF, and BM groups (-7.9 +/- 6.0, -8.5 +/- 8.8, and -10.9 +/- 7.6%, P = 0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all three groups. Quantitative positron emission tomography (PET) demonstrated significant decline in fluorodeoxyglucose uptake rate in the LAD territory at follow-up, with no histological, angiographic, or PET perfusion evidence of functional neovascularization. Immunofluorescence failed to demonstrate transdifferentiation of infused cells.


CONCLUSIONS
Intracoronary infusion of mononuclear cells from either BM or G-CSF-mobilized apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size, or perfusion in a swine model of large MI.
de Silva
Ranil
R
Cardiovascular Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, USA. r.desilva@imperial.ac.uk
Raval
Amish N
AN
Hadi
Mohiuddin
M
Gildea
Karena M
KM
Bonifacino
Aylin C
AC
Yu
Zu-Xi
ZX
Yau
Yu Ying
YY
Leitman
Susan F
SF
Bacharach
Stephen L
SL
Donahue
Robert E
RE
Read
Elizabeth J
EJ
Lederman
Robert J
RJ
D000818:Animals; D001781:Blood Component Removal / Q000379:methods; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008279:Magnetic Resonance Imaging; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D049268:Positron-Emission Tomography; D011994:Recombinant Proteins; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome; D020257:Ventricular Remodeling
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor