Biomedical subjects

Wolfram-Hubertus Zimmermann

Publications and source records attributed to Wolfram-Hubertus Zimmermann.

4 recordsLinked to original sources

PubMed2003

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.

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PubMed2002

Cardiac grafting of engineered heart tissue in syngenic rats.

BACKGROUND: Cell grafting has emerged as a novel approach to treat heart diseases refractory to conventional therapy. We hypothesize that survival and functional and electrical integration of grafts may be improved by engineering cardiac tissue constructs in vitro before grafting. METHODS AND RESULTS: Engineered heart tissue (EHT) was reconstituted by mixing cardiac myocytes from neonatal Fischer 344 rats with liquid collagen type I, matrigel, and serum-containing culture medium. EHTs were designed in circular shape (inner/outer diameter: 8/10 mm; thickness: 1 mm) to fit around the circumference of hearts from syngenic rats. After 12 days in culture and before implantation on uninjured hearts, contractile function of EHT was measured under isometric conditions. Baseline twitch tension amounted to 0.34+/-0.03 mN (n=33) and was stimulated by Ca(2+) and isoprenaline to 200+/-12 and 185+/-10% of baseline values, respectively. Despite utilization of a syngenic model immunosuppression (mg/kg BW: azathioprine 2, cyclosporine A 5, methylprednisolone 2) was necessary for EHT survival in vivo. Echocardiography conducted 7, 14, and 28 days after implantation demonstrated no change in left ventricular function compared with pre-OP values (n=9). Fourteen days after implantation, EHTs were heavily vascularized and retained a well organized heart muscle structure as indicated by immunolabeling of actinin, connexin 43, and cadherins. Ultrastructural analysis demonstrated that implanted EHTs surpassed the degree of differentiation reached before implantation. Contractile function of EHT grafts was preserved in vivo. CONCLUSIONS: EHTs can be employed for tissue grafting approaches and might serve as graft material to repair diseased myocardium.

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PubMed2002

3D engineered heart tissue for replacement therapy.

Myocardial infarction results in irreversible loss of cardiac myocytes and heart failure. Tissue or cell grafting offers the prospect of reintroducing contractile elements into impaired hearts. However, implanted cardiac myocytes remain physically and electrically isolated from the viable myocardium. Accordingly, the proof of increased contractile function attributable specifically to cell grafting procedures is sparse. Over the last few years, we have developed a new method to generate three-dimensional engineered heart tissue (EHTs) in vitro from embryonic chick or neonatal rat cardiac myocytes. EHTs comprise functional and morphological properties of intact myocardium. We hypothesized that EHTs, preformed in vitro into suitable geometric forms, represent appropriate graft material for in vivo tissue repair with advantages over isolated cells. Herein we describe initial results from implantation experiments of EHTs in the peritoneum of Fisher 344 rats. EHTs survived for at least 14 days, maintained a network of differentiated cardiac myocytes, and were strongly vascularized. Thus, the present study provides the first evidence for the general feasibility of EHTs as material for a novel tissue replacement approach.

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PubMed2002

Cardiac tissue engineering.

Recent progress in implantations of differentiated cardiac and non-cardiac cells as well as adult stem cells into the heart suggests that the irreversible loss of viable cardiac myocytes that occurs during myocardial infarction can be at least partly substituted. We evaluated an alternative approach by reconstituting cardiac tissue grafts in vitro and implanting them as spontaneously and coherently contracting tissues. For this purpose we have optimized a method to generate ring-shaped three-dimensional engineered heart tissue (EHT) in vitro from neonatal rat cardiac myocytes. When subjected to isometric force measurements in organ baths, electrically stimulated EHTs exhibit a Frank-Starling behavior, a positive inotropic response to increases in extracellular calcium, a positive inotropic and lusitropic response to isoprenaline, and a negative inotropic response to the muscarinic agonist carbachol ('accentuated antagonism'). Twitch tension under maximal calcium amounts to 1-2 mN/ mm2. Importantly, passive (resting) tension is low, yielding a ratio of active/passive tension of approximately 1.5 under basal and 14 under maximal calcium. Morphologically, EHTs represent a highly interconnected three-dimensional network of cardiac myocytes resembling loose cardiac tissue with a high fraction of binucleated cardiac myocytes, strong eosin staining and elongated centrally located nuclei. Electron microscopy demonstrated well developed sarcomeric structures, T-tubules, SR vesicles, T-tubule-SR-junctions, all types of intercellular connective structures, and a basement membrane. Thus, EHTs comprise functional and morphological properties of intact, ventricular myocardium. First implantation experiments of EHTs in the peritoneum of Fischer 344 rats showed that EHTs survived for at least 14 days, maintained a network of differentiated cardiac myocytes, and were strongly vascularized. Thus, EHTs may serve as material for a novel tissue replacement approach.

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