Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

• Published in: Experimental cell research Vol. 316; no. 11; pp. 1804 - 1815
• Main Authors: De Siena, Rocco, Balducci, Luigi, Blasi, Antonella, Montanaro, Manuela Gessica, Saldarelli, Marilisa, Saponaro, Vittorio, Martino, Carmela, Logrieco, Gaetano, Soleti, Antonio, Fiobellot, Simona, Madeddu, Paolo, Rossi, Giacomo, Ribatti, Domenico, Crovace, Antonio, Cristini, Silvia, Invernici, Gloria, Parati, Eugenio Agostino, Alessandri, Giulio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2010; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; ACTIN; ANGIOGENESIS; Animals; APOPTOSIS; ARTERIES; BLOOD PRESSURE; Body fat; BONE MARROW; Cardiomyocytes; CARDIOVASCULAR DISEASES; Cell Differentiation; Cell growth; Cell Proliferation; Cells, Cultured; Endothelial Cells - pathology; Endothelial Cells - physiology; Fat; FATS; Female; GLUCOSE; HEART; Heart - physiology; Heart attacks; Heart infarct; HISTOLOGY; Hogs; Humans; IN VITRO; In Vitro Techniques; IN VIVO; INFLAMMATION; LYMPHOKINES; MESENTERY; Mice; MONOCYTES; MORPHOGENESIS; MUSCLES; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - therapy; Myocytes, Cardiac - pathology; Myocytes, Cardiac - physiology; Neovascularization, Physiologic; Omentum; Omentum - cytology; Paracrine Communication; PICRIC ACID; Proteins; Regeneration - physiology; Stromal cells; Stromal Cells - cytology; Stromal Cells - physiology; Stromal Cells - transplantation; SWINE; Transplantation; NT; HdMECs; HR; Omentum; Transplantation; FT; LVSF%DSE; FOStCs-CM; DBP; MD; TNP; HCs; MCs; SBP; EFa; ADStCs; BM-MSCs; SMA; FOStCs; Heart infarct; IVA; Stromal cells; Fat; NG; LVSF; HG
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2010.02.009

Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50 × 10 6 of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.