Survival and function of bioengineered cardiac grafts

Introduction-Patients with congenital heart disease frequently require graf t material for repair of cardiac defects. However, currently available graf ts lack growth potential and are noncontractile and thrombogenic. We have d eveloped a viable cardiac graft that contracts spontaneously in tissue cult ure by seeding cells derived from fetal rat ventricular muscle into a biode gradable material. We report our investigations of the in vitro and in vivo survival and function of this bioengineered cardiac graft. Methods and Results-A cardiomyocyte-enriched cell inoculum derived from fet al rat ventricular muscle was seeded into a piece of Gelfoam (Upjohn, Ontar io, Canada), a biodegradable gelatin mesh, to form the graft. For in vitro studies, growth patterns of the cells within the graft were evaluated by co nstructing growth curves and by histologic examination; in in vivo studies, the graft was cultured for 7 days and then implanted either into the subcu taneous tissue of adult rat legs or onto myocardial scar tissue in a cryoin jured rat heart. Five weeks later, the graft was studied histologically. Th e inoculated cells attached to the gelatin mesh and grew in 3 dimensions in tissue culture, forming a beating cardiac graft. In both the subcutaneous tissue and the myocardial scar, blood vessels grew into the graft from the surrounding tissue. The graft implanted into the subcutaneous tissue contra cted regularly and spontaneously. When implanted onto myocardial scar tissu e, the cells within the graft survived and formed junctions with the recipi ent heart cells. Conclusions-Fetal rat ventricular cells can grow 3-dimensionally in a gelat in mesh. The cells in the graft formed cardiac tissue and survived and cont racted spontaneously both in tissue culture and after subcutaneous implanta tion. Future versions of this bioengineered cardiac graft may eventually be used to repair cardiac defects.