Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure

Objective(s): Even though the mechanism is not clearly understood, direct intramyocardial cell transplantation has demonstrated potential to treat patients with severe heart failure. We previously reported on the bioengineering of myoblast-based constructs. We investigate here the functional outcome of infarcted hearts treated by implantation of myoblast-seeded scaffolds. Methods: Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection fraction ( 48.3% +/- 1.1%) were randomized to ( 1) implantation of myoblast-seeded polyurethane patches at the site of infarction ( PU-MyoB, n = 11), ( 2) implantation of nonseeded polyurethane patches ( PU, n = 11), ( 3) sham operation ( Sham, n = 12), and ( 4) direct intramyocardial myoblast injection ( MyoB, n = 11). Four weeks later, the functional assessment by echocardiography was repeated, and we additionally performed left ventricular catheterization plus histologic studies. Results: The ejection fraction significantly decreased in the PU ( 39.1% +/- 2.3%; P = .02) and Sham ( 39.9% +/- 3.5%; P = .04) groups, whereas it remained stable in the PU-MyoB ( 48.4% +/- 3.1%) and MyoB ( 47.9% +/- 3.0%) groups during the observation time. Similarly, left ventricular contractility was significantly higher in groups PU-MyoB ( 4960 +/- 266 mm Hg/s) and MyoB ( 4748 +/- 304 mm Hg/s) than in groups PU ( 3909 +/- 248 mm Hg/s, P = .01) and Sham ( 4028 +/- 199 mm Hg/s, P = .01). Immunohistology identified a high density of myoblasts within the seeded scaffolds without any migration toward the host cardiac tissue and no evidence of cardiac cell differentiation. Conclusions: Myoblast-seeded polyurethane scaffolds prevent post-myocardial infarction progression toward heart failure as efficiently as direct intramyocardial injection. The immunohistologic analysis suggests that an indirect mechanism, potentially a paracrine effect, may be assumed.