Multipotent cells of monocytic origin improve damaged heart function.
Recently, we generated cells with multipotent properties from blood monocytes that in vitro differentiate into various somatic cell types. This experimental study investigated whether these programmable cells of monocytic origin (PCMO) succeed to restore left ventricular function after myocardial infarction (MI). PCMO were generated from monocytes by exposition to RPMI medium containing M-CSF and IL-3 for 6 days. MI was induced in female Lewis rats ligating the left coronary artery. PCMO of male Lewis donors were injected either intramyocardially (i.my.) or intravenously (i.v.) 24 h or 6 days post-infarction. Hemodynamic assessment after 60 days demonstrated significant improvement of left ventricular function following i.my. transplantation of PCMO as well as early (24 h post-infarction) i.v. application while nonmodulated monocytes failed to restore heart function. The Y-chromosome-specific SRY gene of male donor PCMO was detected exclusively in infarcted hearts of animals, which demonstrated improved cardiac function. Subdivision of infarcted hearts by microdissection localized the SRY gene-containing department to the left ventricle adjacent to the infarcted area whereas the right ventricle remained negative. Successful generation of PCMO in access numbers allows their autologous use as a new additive treatment for early restoration of cardiac function after MI.
Dresske
B
B
Department of General and Thoracic Surgery, University of Schleswig-Holstein, Campus Kiel, Germany. BDresske@gmx.de
El Mokhtari
N E
NE
Ungefroren
H
H
Ruhnke
M
M
Plate
V
V
Janssen
D
D
Siebert
R
R
Reinecke
A
A
Simon
R
R
Fandrich
F
F
D000818:Animals; D002196:Capillaries / Q000473:pathology; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D006334:Heart Function Tests; D006439:Hemodynamics; D008297:Male; D009000:Monocytes / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D016277:Ventricular Function, Left; D014998:Y Chromosome
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse