dc.identifier.uri |
http://dx.doi.org/10.15488/2330 |
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dc.identifier.uri |
http://www.repo.uni-hannover.de/handle/123456789/2356 |
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dc.contributor.author |
Kensah, George
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dc.contributor.author |
Lara, Angelica Roa
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dc.contributor.author |
Dahlmann, Julia
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dc.contributor.author |
Zweigerdt, Robert
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dc.contributor.author |
Schwanke, Kristin
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dc.contributor.author |
Hegermann, Jan
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dc.contributor.author |
Skvorc, David
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dc.contributor.author |
Gawol, Anke
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dc.contributor.author |
Azizian, Azadeh
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dc.contributor.author |
Wagner, Stefan
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dc.contributor.author |
Maier, Lars S.
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dc.contributor.author |
Krause, Andreas
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dc.contributor.author |
Dräger, Gerald
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dc.contributor.author |
Ochs, Matthias
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dc.contributor.author |
Haverich, Axel
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dc.contributor.author |
Gruh, Ina
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dc.contributor.author |
Martin, Ulrich
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dc.date.accessioned |
2017-11-17T09:49:37Z |
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dc.date.available |
2017-11-17T09:49:37Z |
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dc.date.issued |
2013 |
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dc.identifier.citation |
Kensah, G.; Lara, A.R.; Dahlmann, J.; Zweigerdt, R.; Schwanke, K. et al.: Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro. In: European Heart Journal 34 (2013), Nr. 15, S. 1134-1146. DOI: https://doi.org/10.1093/eurheartj/ehs349 |
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dc.description.abstract |
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. |
eng |
dc.language.iso |
eng |
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dc.publisher |
Oxford : Oxford University Press |
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dc.relation.ispartofseries |
European Heart Journal 34 (2013), Nr. 15 |
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dc.rights |
Es gilt deutsches Urheberrecht. Das Dokument darf zum eigenen Gebrauch kostenfrei genutzt, aber nicht im Internet bereitgestellt oder an Außenstehende weitergegeben werden. Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. |
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dc.subject |
Cardiac differentiation |
eng |
dc.subject |
Embryonic stem cells |
eng |
dc.subject |
Induced pluripotent stem cells |
eng |
dc.subject |
Myocardial tissue engineering |
eng |
dc.subject |
ascorbic acid |
eng |
dc.subject |
atrial natriuretic factor |
eng |
dc.subject |
brain natriuretic peptide |
eng |
dc.subject |
collagen fibril |
eng |
dc.subject |
collagen type 1 |
eng |
dc.subject |
connectin |
eng |
dc.subject |
troponin T |
eng |
dc.subject |
animal cell |
eng |
dc.subject |
article |
eng |
dc.subject |
bioartificial heart |
eng |
dc.subject |
bioartificial organ |
eng |
dc.subject |
cell aggregation |
eng |
dc.subject |
cell contact |
eng |
dc.subject |
cell count |
eng |
dc.subject |
cell differentiation |
eng |
dc.subject |
cell maturation |
eng |
dc.subject |
cell survival |
eng |
dc.subject |
cell viability |
eng |
dc.subject |
controlled study |
eng |
dc.subject |
diastolic blood pressure |
eng |
dc.subject |
electric potential |
eng |
dc.subject |
embryonic stem cell |
eng |
dc.subject |
extracellular matrix |
eng |
dc.subject |
fibroblast |
eng |
dc.subject |
genetic selection |
eng |
dc.subject |
heart muscle |
eng |
dc.subject |
heart muscle cell |
eng |
dc.subject |
heart muscle contractility |
eng |
dc.subject |
heart preload |
eng |
dc.subject |
human |
eng |
dc.subject |
human cell |
eng |
dc.subject |
in vitro study |
eng |
dc.subject |
intracellular space |
eng |
dc.subject |
long term survival |
eng |
dc.subject |
mechanical stimulation |
eng |
dc.subject |
mouse |
eng |
dc.subject |
nonhuman |
eng |
dc.subject |
pluripotent stem cell |
eng |
dc.subject |
potassium current |
eng |
dc.subject |
priority journal |
eng |
dc.subject |
sarcomere |
eng |
dc.subject |
sarcomere length |
eng |
dc.subject |
systolic blood pressure |
eng |
dc.subject |
transmission electron microscopy |
eng |
dc.subject |
vascularization |
eng |
dc.subject |
Animals |
eng |
dc.subject |
Ascorbic Acid |
eng |
dc.subject |
Bioprosthesis |
eng |
dc.subject |
Cell Culture Techniques |
eng |
dc.subject |
Cell Enlargement |
eng |
dc.subject |
Cell Line |
eng |
dc.subject |
Gene Expression |
eng |
dc.subject |
Humans |
eng |
dc.subject |
Induced Pluripotent Stem Cells |
eng |
dc.subject |
Mice |
eng |
dc.subject |
Myocardial Contraction |
eng |
dc.subject |
Myocardium |
eng |
dc.subject |
Myocytes, Cardiac |
eng |
dc.subject |
Sarcomeres |
eng |
dc.subject |
Tissue Engineering |
eng |
dc.subject |
Vitamins |
eng |
dc.subject.ddc |
610 | Medizin, Gesundheit
|
ger |
dc.title |
Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro |
eng |
dc.type |
Article |
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dc.type |
Text |
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dc.relation.issn |
0195-668X |
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dc.relation.doi |
https://doi.org/10.1093/eurheartj/ehs349 |
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dc.bibliographicCitation.issue |
15 |
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dc.bibliographicCitation.volume |
34 |
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dc.bibliographicCitation.firstPage |
1134 |
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dc.bibliographicCitation.lastPage |
1146 |
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dc.description.version |
publishedVersion |
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tib.accessRights |
frei zug�nglich |
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