Aged Human Cells Rejuvenated by Cytokine Enhancement of Biomaterials for Surgical Ventricular Restoration

Objectives This study investigated whether cytokine enhancement of a biodegradable patch could restore cardiac function after surgical ventricular restoration (SVR) even when seeded with cells from old donors. Background SVR can partially restore heart size and improve function late after an extensive anterior myocardial infarction. However, 2 limitations include the stiff synthetic patch used and the limited healing of the infarct scar in aged patients. Methods We covalently immobilized 2 proangiogenic cytokines (vascular endothelial growth factor and basic fibroblast growth factor) onto porous collagen scaffolds. We seeded human mesenchymal stromal cells from young (50.0 +/- 8.0 years, N = 4) or old (74.5 +/- 7.4 years, N = 4) donors into the scaffolds, with or without growth factors. The patches were characterized and used for SVR in a rat model of myocardial infarction. Cardiac function was assessed. Results In vitro results showed that cells from old donors grew slower in the scaffolds. However, the presence of cytokines modulated the aging-related p16 gene and enhanced cell proliferation, converting the old cell phenotype to a young phenotype. In vivo studies showed that 28 days after SVR, patches seeded with cells from old donors did not induce functional recovery as well as patches seeded with young cells. However, cytokine-enhanced patches seeded with old cells exhibited preserved patch area, prolonged cell survival, and augmented angiogenesis, and rats implanted with these patches had better cardiac function. The patch became an elastic tissue, and the old cells were rejuvenated. Conclusions This sustained-release, cytokine-conjugated system provides a promising platform for engineering myocardial tissue for aged patients with heart failure. (J Am Coll Cardiol 2012;60:2237-49) (C) 2012 by the American College of Cardiology Foundation