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Erschienen in: Pediatric Cardiology 8/2017

27.07.2017 | Original Article

Effect of Glucose on 3D Cardiac Microtissues Derived from Human Induced Pluripotent Stem Cells

verfasst von: Michael Balistreri, Justin A. Davis, Katherine F. Campbell, André Monteiro Da Rocha, Marjorie C. Treadwell, Todd J. Herron

Erschienen in: Pediatric Cardiology | Ausgabe 8/2017

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Abstract

Maternal hyperglycemia is a risk factor for fetal cardiac anomalies. This study aimed to assess the effect of high glucose on human induced pluripotent stem cell-derived cardiomyocyte self-assembly into 3D microtissues and their calcium handling. Stem cells were differentiated to beating cardiomyocytes using established protocols. On the final day of the differentiation process, cells were treated with control media, 12 mM glucose, or 12 mM mannitol (an osmolality control). Once beating, the cardiac cells were dissociated with trypsin, collected, mixed with collagen, and plated into custom-made silicone micro molds in order to generate 3D cardiac microtissues. A time-lapse microscope took pictures every 4 h to quantify the kinetics of cellular self-assembly of 3D cardiac tissues. Fiber widths were recorded at 4-h intervals and plotted over time to assess cardiomyocyte 3D fiber self-assembly. Microtissue calcium flux was recorded with optical mapping by pacing microtissues at 0.5 and 1.0 Hz. Exposure to high glucose impaired the ability of cardiomyocytes to self-assemble into compact microtissues, but not their ability to spontaneously contract. Glucose-exposed cardiomyocytes took longer to self-assemble and finished as thicker fibers. When cardiac microtissues were paced at 0.5 and 1.0 Hz, those exposed to high glucose had altered calcium handling with shorter calcium transient durations, but larger amplitudes of the calcium transient when compared to controls. Additional studies are needed to elucidate a potential mechanism for these findings. This model provides a novel method to assess the effects of exposures on the cardiomyocytes’ intrinsic abilities for organogenesis in 3D.
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Metadaten
Titel
Effect of Glucose on 3D Cardiac Microtissues Derived from Human Induced Pluripotent Stem Cells
verfasst von
Michael Balistreri
Justin A. Davis
Katherine F. Campbell
André Monteiro Da Rocha
Marjorie C. Treadwell
Todd J. Herron
Publikationsdatum
27.07.2017
Verlag
Springer US
Erschienen in
Pediatric Cardiology / Ausgabe 8/2017
Print ISSN: 0172-0643
Elektronische ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-017-1698-2

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