Tissue Engineering von Herzklappen und Myokard

Abstract

Cardiac function, including the heart muscle and valves, can be severely altered by congenital and acquired heart diseases. Several graft materials are currently used to replace diseased cardiac tissue and valvular segments. Implantable grafts are either non-vital or can trigger an immune response which leads to graft calcification and degeneration. None of the existing grafts have the ability to remodel and grow in tandem with the physiological growth of a child and therefore require re-operation. Novel approaches such as tissue engineering have emerged as possible alternatives for cardiac reconstruction. The main concept of tissue engineering includes the use of biological and artificial scaffolds that form the shape of the organ structures for subsequent tissue replacement, which will provide absolute biocompatibility, no thrombogenicity, no teratogenicity, long-term durability and growth.Heart valve tissue engineering represents an important field especially in pediatric patients with valve pathologies. In order to create an autologous valve equivalent myofibroblasts and/or endothelial cells are seeded on specially designed scaffolds. Here we describe the different types of cell sources and different types of matrices currently used in heart valve tissue engineering. Valve manufacture is carried out in specially designed bioreactors providing physiological conditions. The number of clinical studies using tissue engineered valves is still limited; however, several promising results have already demonstrated their durability and ability to grow.Myocardial tissue engineering aims to repair, replace and regenerate damaged cardiac tissue using tissue constructs created ex vivo. Conceivable indications for clinical application of tissue engineered myocardial-implant substitutes include ischemic cardiomyopathies, as well as right ventricular outflow tract reconstruction in patients with congenital heart diseases. Therapeutic application of functional (contractile) tissue engineered heart muscle appears feasible once key issues such as identification of the suitable human cell source, large scale expansion and suitable scaffolds are solved. In addition, the present article discusses the importance of vascularization as an important prerequisite for successful bio-artificial myocardial tissue.Further experimental and clinical research on cardiovascular tissue engineering is felt to be of great importance for others as well as for us in order to create an ideal heart valve/myocardial substitute and help our patients with advanced cardiac pathologies.

Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease

“…[11,12] Successful preclinical studies using prosthetic valve leaflets and swine intestinal submucosa conduits seeded with autologous endothelial cells (ECs)/endothelial progenitor cells (EPCs) [13,14] have been followed by first-in-human studies that confirmed feasibility and advantages of endothelialized grafts. [15,16] Despite the observed improvements of this conduit endothelialisation strategy, the physiological characteristics remained suboptimal in comparison to native vessels, due to the lack of vascular smooth muscle cells (VSMCs). VSMCs are crucial in vessel structure and function; nonetheless, few studies have tested the in vivo potential of tissue-engineered vascular grafts (TEVG) repopulated with VSMCs.…”

Stamm- und progenitorzellbasierte Therapieansätze

“…Hierzu wird auch auf die Beiträge in Herz, Heft 5 verwiesen, die sich mit allgemeinen Aspekten (Maisch [134]) und der gezielten, meist chirurgischen Anwendung verschiedener Zellpopulationen der Regenerationstherapie befassen (Bergmann et al [135], Cabotari et al [136], Kaminski et al [137] (2007) …”

Regeneration in der Kardiologie - Innovation oder Illusion?

“…Kaminski et al [7] favorisieren die intramyokardiale Stammzelltherapie; Cebotari und Haverich [3] berichten über beeindruckende erste Erfolge beim "Tissue-Engineering von Herzklappen und Myokardgewebe". Becher et al [1] beschreiben "EC-like cells und endothelial outgrow cells (EOCs)" als Teil einer zeitlich begrenzten Reendothelialisierung der Läsion und als Platzhalter der Regeneration an der geschädigten Gefäßwand.…”