Wolfram-Hubertus Zimmermann

Engineered heart tissue for regeneration of diseased hearts

Cardiac tissue engineering aims at providing contractile heart muscle constructs for replacement therapy in vivo. At present, most cardiac tissue engineering attempts utilize heart cells from embryonic chicken and neonatal rats and scaffold materials. Over the past years our group has developed a novel technique to engineer collagen/matrigel-based cardiac muscle constructs, which we termed engineered heart tissue (EHT). EHT display functional and morphological properties of differentiated heart muscle and can be constructed in different shape and size from collagen type I, extracellular matrix proteins (Matrigel((R))), and heart cells from neonatal rats and embryonic chicken. First implantation studies in syngeneic Fischer 344 rats provided evidence of EHT survival and integration in vivo. This review will focus on our experience in tissue engineering of cardiac muscle. Mainly, EHT construction, matrix requirements, potential applications of different cell types including stem cells, and our first implantation experiences will be discussed. Despite many critical and unresolved questions, we believe that cardiac tissue engineering in general has an interesting perspective for the replacement of malfunctioning myocardium and reconstruction of congenital malformations.

Cardiac Tissue Engineering for Replacement Therapy

Cell therapy is a new concept to repair diseased organs. For patients with myocardial infarction, heart failure, and congenital heart diseases cell based therapies might represent a potential cure. The field can be subdivided into two principally different approaches: (1) Implantation of isolated cells and (2) implantation of in vitro engineered tissue constructs. This review will focus on the latter approach. Cardiac tissue engineering comprises the fields of material sciences and cell biology. In general, scaffold materials such as gelatin, collagen, alginate, or synthetic polymers and cardiac cells are utilized to reconstitute tissue-like constructs in vitro. Ideally, these constructs display properties of native myocardium such as coherent contractions, low diastolic tension, and syncytial propagation of action potentials. To be applicable for surgical repair of diseased myocardium engineered tissue constructs should have the propensity to integrate and remain contractile in vivo. Size and mechanical properties of engineered constructs are critical for surgical repair of large tissue defects. Successful application of tissue engineering in men will depend on the utilization of an autologous or non-immunogeneic cell source and scaffold material to avoid life long immunosuppression. This review will give an overview of recent approaches in cardiac tissue engineering and its first applications in vivo. We will discuss materials and cell sources for cardiac tissue engineering. Further, principle obstacles will be addressed. Cardiac tissue engineering for replacement therapy has an intriguing perspective, but is in its early days. Its true value remains to be thoroughly evaluated.