Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro

Medientyp: E-Artikel; Sonstige Veröffentlichung

Titel: Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro

Beteiligte: Kensah, George [VerfasserIn]; Lara, Angelica Roa [VerfasserIn]; Dahlmann, Julia [VerfasserIn]; Zweigerdt, Robert [VerfasserIn]; Schwanke, Kristin [VerfasserIn]; Hegermann, Jan [VerfasserIn]; Skvorc, David [VerfasserIn]; Gawol, Anke [VerfasserIn]; Azizian, Azadeh [VerfasserIn]; Wagner, Stefan [VerfasserIn]; Maier, Lars S. [VerfasserIn]; Krause, Andreas [VerfasserIn]; Dräger, Gerald [VerfasserIn]; Ochs, Matthias [VerfasserIn]; Haverich, Axel [VerfasserIn]; Gruh, Ina [VerfasserIn]; Martin, Ulrich [VerfasserIn]

Erschienen: Oxford : Oxford University Press, 2013

Ausgabe: published Version

Sprache: Englisch

DOI: https://doi.org/10.15488/2330; https://doi.org/10.1093/eurheartj/ehs349

ISSN: 0195-668X

Schlagwörter: troponin T ; Cardiac differentiation ; article ; Myocardial tissue engineering ; embryonic stem cell ; Animals ; cell contact ; priority journal ; bioartificial heart ; collagen fibril ; collagen type 1 ; heart muscle cell ; heart muscle contractility ; human cell ; mechanical stimulation ; sarcomere length ; atrial natriuretic factor ; heart muscle ; cell count ; long term survival ; in vitro study ; cell maturation ; nonhuman ; extracellular matrix ; [...]

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Beschreibung: AimsWe explored the use of highly purified murine and human pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) to generate functional bioartificial cardiac tissue (BCT) and investigated the role of fibroblasts, ascorbic acid (AA), and mechanical stimuli on tissue formation, maturation, and functionality.Methods and resultsMurine and human embryonic/induced PSC-derived CMs were genetically enriched to generate three-dimensional CM aggregates, termed cardiac bodies (CBs). Addressing the critical limitation of major CM loss after single-cell dissociation, non-dissociated CBs were used for BCT generation, which resulted in a structurally and functionally homogenous syncytium. Continuous in situ characterization of BCTs, for 21 days, revealed that three critical factors cooperatively improve BCT formation and function: both (i) addition of fibroblasts and (ii) ascorbic acid supplementation support extracellular matrix remodelling and CB fusion, and (iii) increasing static stretch supports sarcomere alignment and CM coupling. All factors together considerably enhanced the contractility of murine and human BCTs, leading to a so far unparalleled active tension of 4.4 mN/mm2 in human BCTs using optimized conditions. Finally, advanced protocols were implemented for the generation of human PSC-derived cardiac tissue using a defined animal-free matrix composition.ConclusionBCT with contractile forces comparable with native myocardium can be generated from enriched, PSC-derived CMs, based on a novel concept of tissue formation from non-dissociated cardiac cell aggregates. In combination with the successful generation of tissue using a defined animal-free matrix, this represents a major step towards clinical applicability of stem cell-based heart tissue for myocardial repair. © 2013 The Author.

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Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro - [published Version]

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