Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure.
OBJECTIVE
Cellular cardiomyoplasty using skeletal myoblasts or angiopoietic progenitor cells offers a promising approach for the treatment of ischemic heart failure. Although several studies have shown encouraging results in acute myocardial infarction, the efficacy of cell therapy using skeletal myoblasts and angiopoietic progenitor cells in chronic ischemic heart disease remains undetermined.


METHODS
Ischemic heart failure was induced by left anterior descending coronary artery ligation in nude rats: (1) Culture medium, (2) homologous skeletal myoblasts (SM), (3) human AC-133+ cells (SC), and (4) both skeletal myoblasts and AC-133+ cells (Comb) were injected in the infarct (SM) and peri-infarct area (SC) 4 weeks after infarction. Assessment of myocardial function included echocardiography 4 weeks after cell delivery. Histology was based on quantification of myocardial fibrosis, apoptosis, and capillary density.


RESULTS
Left ventricular dilatation was attenuated and ejection fraction improved significantly after cell transplantation (SM: 59.4% +/- 8.8%, SC: 60.3% +/- 6.6%, Comb: 68.2% +/- 5.6% vs control: 41.5% +/- 7.4%, P = .0013). Quantification of scar tissue showed a significant reduction of infarct area in cell-treated animals (SM: 22.3% +/- 9.1%, SC: 19.8% +/- 7.6%, Comb: 13.2% +/- 5.8% vs controls: 36.5% +/- 8.2%, P = .008). Improvement of myocardial function was associated with reduced apoptotic index (SM: 3.2% +/- 0.9%, SC: 3.1% +/- 0.6%, Comb: 1.8% +/- 0.8% vs controls: 10.3% +/- 1.6%, P = .0002) and increased vascular density (SM: 5.2 +/- 1.2, SC: 8.3 +/- 1.8, Comb: 12.3 +/- 2.3, controls: 1.9 +/- 0.3, all capillary vessels/high-power field, P = .007) in animals after cellular cardiomyoplasty.


CONCLUSIONS
Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells results in ventricular function improvement, reduction of scar size and myocardial apoptosis, and increased neoangiogenesis in chronic ischemia. Clinical studies are warranted to prove this new therapeutic concept.
Bonaros
Nikolaos
N
Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria. nikolaos.bonaros@uibk.ac.at
Rauf
Rauend
R
Wolf
Dominik
D
Margreiter
Eva
E
Tzankov
Alexandar
A
Schlechta
Bernhard
B
Kocher
Alfred
A
Ott
Harald
H
Schachner
Thomas
T
Hering
Steffen
S
Bonatti
Johannes
J
Laufer
Guenther
G
D000818:Animals; D017209:Apoptosis; D002908:Chronic Disease; D006333:Heart Failure / Q000473:pathology* / Q000601:surgery*; D008297:Male; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D017202:Myocardial Ischemia / Q000473:pathology* / Q000601:surgery*; D018919:Neovascularization, Physiologic; D051381:Rats; D033581:Stem Cell Transplantation