Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle

Objectives: Most tissue-engineering approaches to restore injured heart muscle result in distortion of left ventricular geometry. In the present study we suggest seeding embryonic stem cells in a liquid matrix for myocardial restoration. Methods: Undifferentiated green fluorescent protein-labeled mouse embryonic stem cells (2 x 10(6)) were seeded in Matrigel (B&D, Bedford, Mass). In a Lewis rat heterotopic heart transplant model an intramural left ventricular pouch was fashioned after ligation of the left anterior descending coronary artery. The liquid mixture (0.125 mL) was injected in the resulting infarcted area within the pouch and solidified within a few minutes after transplantation (37degreesC). Five recipient groups were formed: transplanted healthy hearts (group I), infarcted control hearts (group II), matrix recipients alone (group III), the study group that received matrix plus cells (group IV), and a group that received embryonic stem cells alone (group V). After echocardiography 2 weeks later, the hearts were harvested and stained for green fluorescent protein and cardiac muscle markers (connexin 43 and alpha-sarcomeric actin). Results: The graft formed a sustained structure within the injured area and prevented ventricular wall thinning. The inoculated cells remained viable and expressed connexin 43 and alpha-sarcomeric actin. Fractional shortening and regional contractility were better in animals that received bioartificial tissue grafts compared with control animals (infarcted, matrix only, and embryonic stem cells only: group I, 17.0% +/- 3.5%; group II, 6.6% +/- 2.1%; group III, 10.3% +/- 2.2%; group IV, 14.5% +/- 2.5%; and group V, 7.8% +/- 1.8%). Conclusions: Liquid bioartificial tissue containing embryonic stem cells constitutes a powerful new approach to restoring injured heart muscle without distorting its geometry and structure.