Epicardial adipose stem cell sheets results in greater post-infarction survival than intramyocardial injections

• Published in: Cardiovascular research Vol. 91; no. 3; pp. 483 - 491
• Main Authors: Hamdi, Hadhami, Planat-Benard, Valérie, Bel, Alain, Puymirat, Etienne, Geha, Raghed, Pidial, Laetitia, Nematalla, Hany, Bellamy, Valérie, Bouaziz, Philippe, Peyrard, Séverine, Casteilla, Louis, Bruneval, Patrick, Hagège, Albert A., Agbulut, Onnik, Menasché, Philippe
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-08-2011
• Subjects: Angiogenic Proteins - metabolism; Animals; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Disease Models, Animal; Extracellular Matrix Proteins - metabolism; Female; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Injections; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - surgery; Myocardium - metabolism; Myocardium - pathology; Neovascularization, Physiologic; Pericardium - metabolism; Pericardium - pathology; Rats; Rats, Wistar; Recovery of Function; Stem Cell Transplantation - methods; Stem Cells - metabolism; Subcutaneous Fat - cytology; Time Factors; Tissue Scaffolds; Transfection; Ventricular Function, Left; Ventricular Remodeling; Cell sheet; Extracellular matrix; Adipose-derived stromal cells; Transplantation; Chronic ischaemic heart failure; Temperature-responsive surface
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvr099

Aims
Intramyocardial injections of cells can damage tissue and enhance dissociation-induced cell death. We assessed whether epicardial delivery of cell sheets could overcome these issues in a rat model of chronic myocardial infarction.
Methods and results
Eighty-two rats that had undergone coronary ligation and simultaneous harvest of fat tissue to yield the adipose-derived stromal cell (ADSC) fraction were randomized 1 month after infarction to receive injections of either control medium (n= 24) or 10 × 106 autologous ADSC (n= 37) or the epicardial deposit, onto the infarcted area, of a trilayered ADSC sheet (10 × 106, n= 21) prepared by culturing cells on temperature-sensitive dishes. Some treated rats received green fluorescent protein labelled ADSC. Survival, function, and cell engraftment were blindly assessed after 2 months. Prior to implantation, cell sheets and suspended cells were assessed for the expression of extracellular matrix constituents and molecules involved in angiogenesis and cardiac remodelling. The survival rate of rats receiving the cell sheets was significantly higher than after cell injections (73 vs. 41%, P = 0.01). This correlated with the absence of left ventricular (LV) remodelling in the cell sheet group, as end-diastolic volume only increased by 2.8% compared with baseline [95% confidence interval (CI): −18.7%; +30.0%, P = 0.81] vs. increases of 25.9% (−0.4%; +59.2%, P = 0.05) and 51.2% (+18.6%; +92.8, P = 0.001) in the cell and medium injection groups, respectively. Sheets also resulted in a greater cell engraftment possibly related to the greater expression of extracellular matrix constituents.
Conclusion
The better preservation of LV geometry afforded by ADSC sheets is associated with increased survival and engraftment, which supports the concept of an epicardial delivery of cell-seeded biomaterials.