BACKGROUND: Using a swine model of postinfarction left ventricle (LV) remodeling, we investigated marrow-derived, multipotent progenitor cell (MPC) transplantation into hearts with acute myocardial infarction (AMI) via a novel transarterial catheter. METHODS AND RESULTS: The left anterior descending coronary artery was balloon-occluded after percutaneous transluminal angiography to generate AMI (60-minute no-flow ischemia). The transarterial catheter was then placed in the same coronary artery, and either 50x10(6) MPCs (cell group, n=6) or saline (control, n=6) was injected into the border zone (BZ) myocardium. LV function was assessed by magnetic resonance imaging before AMI and at 1 and 4 weeks after AMI, whereas myocardial energy metabolism was assessed by (31)P-magnetic resonance spectroscopy at week 4. One week after AMI, the ejection fraction was significantly reduced in both groups from a baseline of approximately 50% to 31.3+/-3.9% (cell group) and 33.3+/-3.1% (control). However, at week 4, the cell group had a significant recovery in ejection fraction. The functional improvements were accompanied by a significant improvement in myocardial bioenergetics. Histologic data demonstrated a 0.55% cell engraftment rate 4 weeks after MPC transplantation. Only 2% of engrafted cells were costaining positive for cardiogenic markers. Vascular density in the BZ was increased in the cell group. Conditioned medium from cultured MPCs contained high levels of vascular endothelial growth factor, which was increased in response to hypoxia. MPCs cocultured with cardiomyocytes inhibited changes in cardiomyocyte mitochondrial membrane potential and cytochrome c release induced by tumor necrosis factor-alpha. CONCLUSIONS: Thus, a paracrine effect may contribute significantly to the observed therapeutic effects of MPC transplantation.
BACKGROUND: Using a swine model of postinfarction left ventricle (LV) remodeling, we investigated marrow-derived, multipotent progenitor cell (MPC) transplantation into hearts with acute myocardial infarction (AMI) via a novel transarterial catheter. METHODS AND RESULTS: The left anterior descending coronary artery was balloon-occluded after percutaneous transluminal angiography to generate AMI (60-minute no-flow ischemia). The transarterial catheter was then placed in the same coronary artery, and either 50x10(6) MPCs (cell group, n=6) or saline (control, n=6) was injected into the border zone (BZ) myocardium. LV function was assessed by magnetic resonance imaging before AMI and at 1 and 4 weeks after AMI, whereas myocardial energy metabolism was assessed by (31)P-magnetic resonance spectroscopy at week 4. One week after AMI, the ejection fraction was significantly reduced in both groups from a baseline of approximately 50% to 31.3+/-3.9% (cell group) and 33.3+/-3.1% (control). However, at week 4, the cell group had a significant recovery in ejection fraction. The functional improvements were accompanied by a significant improvement in myocardial bioenergetics. Histologic data demonstrated a 0.55% cell engraftment rate 4 weeks after MPC transplantation. Only 2% of engrafted cells were costaining positive for cardiogenic markers. Vascular density in the BZ was increased in the cell group. Conditioned medium from cultured MPCs contained high levels of vascular endothelial growth factor, which was increased in response to hypoxia. MPCs cocultured with cardiomyocytes inhibited changes in cardiomyocyte mitochondrial membrane potential and cytochrome c release induced by tumor necrosis factor-alpha. CONCLUSIONS: Thus, a paracrine effect may contribute significantly to the observed therapeutic effects of MPC transplantation.
Authors: Birgit Assmus; Jörg Honold; Volker Schächinger; Martina B Britten; Ulrich Fischer-Rasokat; Ralf Lehmann; Claudius Teupe; Katrin Pistorius; Hans Martin; Nasreddin D Abolmaali; Torsten Tonn; Stefanie Dimmeler; Andreas M Zeiher Journal: N Engl J Med Date: 2006-09-21 Impact factor: 91.245
Authors: Nicolas Noiseux; Massimiliano Gnecchi; Marco Lopez-Ilasaca; Lunan Zhang; Scott D Solomon; Arjun Deb; Victor J Dzau; Richard E Pratt Journal: Mol Ther Date: 2006-09-11 Impact factor: 11.454
Authors: Lepeng Zeng; Qingsong Hu; Xiaohong Wang; Abdul Mansoor; Joseph Lee; Julia Feygin; Ge Zhang; Piradeep Suntharalingam; Sherry Boozer; Abner Mhashilkar; Carmelo J Panetta; Cory Swingen; Robert Deans; Arthur H L From; Robert J Bache; Catherine M Verfaillie; Jianyi Zhang Journal: Circulation Date: 2007-03-26 Impact factor: 29.690
Authors: Xiaohong Wang; Qingsong Hu; Yasuhiro Nakamura; Joseph Lee; Ge Zhang; Arthur H L From; Jianyi Zhang Journal: Stem Cells Date: 2006-04-13 Impact factor: 6.277
Authors: Qingsong Hu; Xiaohong Wang; Joseph Lee; Abdul Mansoor; Jingbo Liu; Lepeng Zeng; Cory Swingen; Ge Zhang; Julia Feygin; Koichi Ochiai; Toni L Bransford; Arthur H L From; Robert J Bache; Jianyi Zhang Journal: Am J Physiol Heart Circ Physiol Date: 2006-03-31 Impact factor: 4.733
Authors: Marcello Rota; Jan Kajstura; Toru Hosoda; Claudia Bearzi; Serena Vitale; Grazia Esposito; Grazia Iaffaldano; M Elena Padin-Iruegas; Arantxa Gonzalez; Roberto Rizzi; Narissa Small; John Muraski; Roberto Alvarez; Xiongwen Chen; Konrad Urbanek; Roberto Bolli; Steven R Houser; Annarosa Leri; Mark A Sussman; Piero Anversa Journal: Proc Natl Acad Sci U S A Date: 2007-10-26 Impact factor: 11.205
Authors: Claudia Bearzi; Marcello Rota; Toru Hosoda; Jochen Tillmanns; Angelo Nascimbene; Antonella De Angelis; Saori Yasuzawa-Amano; Irina Trofimova; Robert W Siggins; Nicole Lecapitaine; Stefano Cascapera; Antonio P Beltrami; David A D'Alessandro; Elias Zias; Federico Quaini; Konrad Urbanek; Robert E Michler; Roberto Bolli; Jan Kajstura; Annarosa Leri; Piero Anversa Journal: Proc Natl Acad Sci U S A Date: 2007-08-20 Impact factor: 11.205
Authors: Bryon A Tompkins; Wayne Balkan; Johannes Winkler; Mariann Gyöngyösi; Georg Goliasch; Francisco Fernández-Avilés; Joshua M Hare Journal: Circ Res Date: 2018-03-30 Impact factor: 17.367
Authors: Jacqueline S Wendel; Lei Ye; Pengyuan Zhang; Robert T Tranquillo; Jianyi Jay Zhang Journal: Tissue Eng Part A Date: 2014-02-06 Impact factor: 3.845