Remuscularizing failing hearts with tissue engineered myocardium

Abstract

Supporting or even replacing diseased myocardium with in vitro engineered heart muscle may become a viable option for patients with heart failure. The key to success will be to (1) generate human heart muscle equivalents in vitro, (2) integrate the latter into a failing heart, (3) ensure long-term functional competence of the grafts, and (4) prevent unwanted effects including arrhythmias, inflammation/rejection, and tumor formation. Several promising tissue engineering technologies have already been developed and are presently being tested in animal models. The rapidly evolving field of human stem cell biology has in parallel identified unique cell sources of potential clinical relevance. Somatic cell reprogramming and nontransduced, nonembryonic pluripotent stem cells may be of particular interest to eventually provide patient-specific cells and tissues. Yet, limited cardiac differentiation and cell immaturity still restrict a broad application of any stem cell type in cardiac muscle engineering. Bioreactor technologies, transgenic "optimization," and growth factor, as well as physical conditioning, have been used to address these caveats. This review summarizes different tissue engineering modalities, speculates on potential clinical uses, provides an overview on cell sources that may ultimately facilitate a patient-specific application, and discusses limitations of tissue engineering-based myocardial repair.