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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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.
Total Authors: 10
Document type: Journal article
Source: PLoS One; v. 12, n. 4 APR 27 2017.
Web of Science Citations: 3
Abstract

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 4x10 6 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 pASCsinduced 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. (AU)

FAPESP's process: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther
Grantee:José Eduardo Krieger
Support Opportunities: Research Projects - Thematic Grants