3D engineered heart tissue for replacement therapy

Eschenhagen, Thomas; Didié, Michael; Münzel, Felix; Schubert, Philipp; Schneiderbanger, Karin; Zimmermann, Wolfram‐Hubertus

doi:10.1007/s003950200043

Cited by 78 publications

(71 citation statements)

References 20 publications

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“…Similar findings were made in stacked cell sheets from neonatal rat hearts (81) and EHTs from human embryonic stem cell (hESC)-derived cardiac myocytes that were mixed with endothelial cells (12,94). Vascularization was extensive a few weeks after implantation onto the heart (21,81,106,109). The exact time course remains insufficiently studied.…”

Section: Cardiac Repair With Engineered Tissues: Results From Animal mentioning

confidence: 56%

Physiological aspects of cardiac tissue engineering

Eschenhagen

Eder

Vollert

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Cardiac tissue engineering aims at repairing the diseased heart and developing cardiac tissues for basic research and predictive toxicology applications. Since the first description of engineered heart tissue 15 years ago, major development steps were directed toward these three goals. Technical innovations led to improved three-dimensional cardiac tissue structure and near physiological contractile force development. Automation and standardization allow medium throughput screening. Larger constructs composed of many small engineered heart tissues or stacked cell sheet tissues were tested for cardiac repair and were associated with functional improvements in rats. Whether these approaches can be simply transferred to larger animals or the human patients remains to be tested. The availability of an unrestricted human cardiac myocyte cell source from human embryonic stem cells or human-induced pluripotent stem cells is a major breakthrough. This review summarizes current tissue engineering techniques with their strengths and limitations and possible future applications.

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Section: Cardiac Repair With Engineered Tissues: Results From Animal mentioning

confidence: 56%

Physiological aspects of cardiac tissue engineering

Eschenhagen

Eder

Vollert

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…17 Earlier studies had shown that EHTs benefit from addition of growth factors. 11 Thus, we performed an initial series of experiments…”

Section: Serum Replacementmentioning

confidence: 99%

Optimizing Engineered Heart Tissue for Therapeutic Applications as Surrogate Heart Muscle

et al. 2006

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Background— Cardiac tissue engineering aims at providing heart muscle for cardiac regeneration. Here, we hypothesized that engineered heart tissue (EHT) can be improved by using mixed heart cell populations, culture in defined serum-free and Matrigel-free conditions, and fusion of single-unit EHTs to multi-unit heart muscle surrogates. Methods and Results— EHTs were constructed from native and cardiac myocyte enriched heart cell populations. The former demonstrated a superior contractile performance and developed vascular structures. Peptide growth factor-supplemented culture medium was developed to maintain contractile EHTs in a serum-free environment. Addition of triiodothyronine and insulin facilitated withdrawal of Matrigel from the EHT reconstitution mixture. Single-unit EHTs could be fused to form large multi-unit EHTs with variable geometries. Conclusions— Simulating a native heart cell environment in EHTs leads to improved function and formation of primitive capillaries. The latter may constitute a preformed vascular bed in vitro and facilitate engraftment in vivo. Serum- and Matrigel-free culture conditions are expected to reduce immunogenicity of EHT. Fusion of single-unit EHT allows production of large heart muscle constructs that may eventually serve as optimized tissue grafts in cardiac regeneration in vivo.

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“…Given these properties, collagen is a potential biomaterial for developing a heart tissue model which was also supported by our findings. Also previous studies have shown that collagen gel supports cardiomyocyte growth in 3D models [15] and has served as a scaffold material in studies aiming to create cardiac muscle constructs [22]. However, collagen gel is typically combined with Matrigel™, a protein mixture secreted by mouse sarcoma cells, and not used alone, as in our study.…”

Section: Discussionmentioning

confidence: 91%

“…The self-isolated collagen was isolated as described previously [15] with some modifications. Briefly, the tails were harvested from adult Sprague Dawley rats and stored at -20°C.…”

Section: Collagen Gelmentioning

confidence: 99%

Analysis of Different Natural and Synthetic Biomaterials to Support Cardiomyocyte Growth

Kerkelä¹,

Kujala²,

Poh³

et al. 2013

J Clin Exp Cardiolog

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The aim of this study was to scan through several biomaterials to find an optimal biomaterial to support the growth of cardiomyocytes. Neonatal rat cardiomyocytes were cultured on polylactide, chitosan, poly (1,8-octanediolco-citric acid), copolymer of poly(ethylene oxide terephthalate) and poly (butylene terephthalate), PuraMatrix™ and collagen. The suitability of biomaterials for cardiomyocyte culture was evaluated based on several parameters. The cells were characterized with time-lapse imaging, immunocytochemistry and LIVE/DEAD ® staining. Collagen gel was the best biomaterial. It supported well the growth, survival and functionality of the cardiomyocytes. Polylactide and chitosan membranes supported the cell growth and survival, but these biomaterials were too stiff for further cardiac applications. In conclusion, collagen gel is a good biomaterial to obtain a 3D structure to model heart tissue.

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3D engineered heart tissue for replacement therapy

Cited by 78 publications

References 20 publications

Physiological aspects of cardiac tissue engineering

Physiological aspects of cardiac tissue engineering

Optimizing Engineered Heart Tissue for Therapeutic Applications as Surrogate Heart Muscle

Analysis of Different Natural and Synthetic Biomaterials to Support Cardiomyocyte Growth

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