Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction

• Published in: PloS one Vol. 12; no. 4; p. e0176412
• Main Authors: Dariolli, Rafael, Naghetini, Marcus V, Marques, Euclydes F, Takimura, Celso K, Jensen, Leonardo S, Kiers, Bianca, Tsutsui, Jeane M, Mathias, Jr, Wilson, Lemos Neto, Pedro A, Krieger, Jose E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.04.2017; Public Library of Science (PLoS)
• Subjects: Adipose Tissue - cytology; Angiotensin-converting enzyme inhibitors; Animals; Bioaccumulation; Biology and Life Sciences; Blood flow; Cardiomyocytes; Collagen; Coronary artery; Coronary Circulation - drug effects; Earth Sciences; Echocardiography; Enalaprilat - pharmacology; Enzyme inhibitors; Female; Fibers; Heart attacks; Heart diseases; Heart failure; Hemodynamics - drug effects; Medical schools; Medicine and Health Sciences; Mesenchymal Stem Cell Transplantation; Mesenchyme; Metoprolol - pharmacology; Myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - therapy; Myocardium; Occlusion; Peptidyl-dipeptidase A; Perfusion; Research and Analysis Methods; Rodents; Skin & tissue grafts; Stem cell transplantation; Stem cells; Stromal cells; Swine; Systematic review; Transplantation; Transplantation, Homologous; Transplants & implants; Ventricular Remodeling - drug effects; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0176412

Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.