OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: Karin Albrecht-Schgoer; Wilfried Schgoer; Johannes Holfeld; Markus Theurl; Dominik Wiedemann; Christina Steger; Rajesh Gupta; Severin Semsroth; Reiner Fischer-Colbrie; Arno G E Beer; Ursula Stanzl; Eva Huber; Sol Misener; Daniel Dejaco; Raj Kishore; Otmar Pachinger; Michael Grimm; Nikolaos Bonaros; Rudolf Kirchmair Journal: Circulation Date: 2012-10-18 Impact factor: 29.690
Authors: Satsuki Fukushima; Steven R Coppen; Joon Lee; Kenichi Yamahara; Leanne E Felkin; Cesare M N Terracciano; Paul J R Barton; Magdi H Yacoub; Ken Suzuki Journal: PLoS One Date: 2008-08-27 Impact factor: 3.240