Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile.
OBJECTIVE
There is increasing evidence that stem cell (SC) mobilization to the heart and their differentiation into cardiac cells is a naturally occurring process. We sought to assess the safety and feasibility of granulocyte-colony stimulating factor (G-CSF) administration in humans to enhance SC mobilization and left ventricle (LV) injury repair during myocardial infarction (MI).


RESULTS
Twenty patients with STEMI (mean age, 61+/-10 years), of whom 14 were submitted to primary percutaneous coronary intervention, were randomized to G-CSF (5 microg/kg/day s.c. for 4 consecutive days) or placebo. At entry and then at months 3 and 6, (99m)Tc-sestamibi gated-SPECT was performed to estimate extension of perfusion defect (PD) and LV function. The study drug was well tolerated and induced a significant increase of white blood count, CD34(+) cells, and CD34(+) cells coexpressing AC133 and VEGFR-2. At follow-up, treated and placebo groups did not differ for the angiographic coronary late loss and showed a similar pattern of PD recovery, whereas in the former at 6 months LVEF and especially LVEDV tended to be relatively higher (P=0.068) and lower (P=0.054), respectively.


CONCLUSIONS
G-CSF administration in acute MI patients was feasible and did not lead to any clinical or angiographic adverse events and resulted in CD34(+) and CD34(+)AC133(+)VEGFR2(+) cell mobilization.
Valgimigli
Marco
M
Section of Cardiology, University of Ferrara and Cardiovascular Research Centre, Arcispedale S. Anna C.rso Giovecca 203, 44100 Ferrara, Italy. vlgmrc@unife.it
Rigolin
Gian Matteo
GM
Cittanti
Corrado
C
Malagutti
Patrizia
P
Curello
Salvatore
S
Percoco
Gianfranco
G
Bugli
Anna Maria
AM
Della Porta
Matteo
M
Bragotti
Letizia Zenone
LZ
Ansani
Lucia
L
Mauro
Endri
E
Lanfranchi
Arnalda
A
Giganti
Melchiore
M
Feggi
Luciano
L
Castoldi
Gianluigi
G
Ferrari
Roberto
R
D018952:Antigens, CD34; D017023:Coronary Angiography; D003326:Coronary Circulation; D023903:Coronary Restenosis / Q000209:etiology; D023921:Coronary Stenosis / Q000628:therapy; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D011994:Recombinant Proteins; D020127:Recovery of Function; D016037:Single-Blind Method; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000628:therapy
D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim