Shaping the heart: structural and functional maturation of iPSC-cardiomyocytes in 3D-micro-scaffolds
Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) represent the best cell source for cardiac regenerative purposes but retain an immature phenotype after differentiation with significant limitations compared to adult cardiomyocytes. Apart from an incomplete cardiomyocyte-specific...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2020
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| In: |
Biomaterials
Year: 2019, Jahrgang: 227, Pages: 119551 |
| ISSN: | 1878-5905 |
| DOI: | 10.1016/j.biomaterials.2019.119551 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1016/j.biomaterials.2019.119551 Verlag: http://www.sciencedirect.com/science/article/pii/S0142961219306507 
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| Verfasserangaben: | Nicole Silbernagel, Arlene Körner, Jakob Balitzki, Mona Jaggy, Sarah Bertels, Benjamin Richter, Marc Hippler, Andrea Hellwig, Markus Hecker, Martin Bastmeyer, Nina D. Ullrich |
| Zusammenfassung: | Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) represent the best cell source for cardiac regenerative purposes but retain an immature phenotype after differentiation with significant limitations compared to adult cardiomyocytes. Apart from an incomplete cardiomyocyte-specific structure and microarchitecture, cells show at the level of Ca2+ signaling only slow Ca2+ release and reuptake properties. Here, we investigated the effect of restructuring single iPSC-CMs in specially designed 3D-micro-scaffolds on cell morphology and Ca2+ handling. Using direct laser writing, rectangular-shaped scaffolds were produced and single iPSC-CMs were seeded into these forms. Structural analyses revealed strong sarcolemmal remodeling processes and myofilament reorientation in 3D-shaped cells leading to enhanced clustered expression of L-type Ca2+ channels and ryanodine receptors and consequently, to faster Ca2+ transient kinetics. Spontaneous beating activity was enhanced and Ca2+ handling was more robust compared to non-patterned cells. Overall, our data demonstrate for the first time significant improvement of Ca2+ signaling properties in reshaped iPSC-CMs indicative of functional maturation by structural remodeling. |
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| Beschreibung: | Available online 19 October 2019 Gesehen am 13.01.2020 |
| Beschreibung: | Online Resource |
| ISSN: | 1878-5905 |
| DOI: | 10.1016/j.biomaterials.2019.119551 |