Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism.
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 50x10(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.
De Siena
Rocco
R
Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari, Italy.
Balducci
Luigi
L
Blasi
Antonella
A
Montanaro
Manuela Gessica
MG
Saldarelli
Marilisa
M
Saponaro
Vittorio
V
Martino
Carmela
C
Logrieco
Gaetano
G
Soleti
Antonio
A
Fiobellot
Simona
S
Madeddu
Paolo
P
Rossi
Giacomo
G
Ribatti
Domenico
D
Crovace
Antonio
A
Cristini
Silvia
S
Invernici
Gloria
G
Parati
Eugenio Agostino
EA
Alessandri
Giulio
G
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D005260:Female; D006321:Heart / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology; D018919:Neovascularization, Physiologic; D009852:Omentum / Q000166:cytology*; D019899:Paracrine Communication; D012038:Regeneration / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D013552:Swine