Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture

Branco, Mariana A.; Cotovio, João P.; Rodrigues, Carlos Alberto Chirano; Vaz, Sandra H.; Fernandes, Tiago G.; Moreira, Leonilde M.; Cabral, Joaquim M. S.; Diogo, Maria Margarida

doi:10.1038/s41598-019-45047-9

Cited by 91 publications

(78 citation statements)

References 59 publications

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“…When the RNA-sequencing data of SOTR cardiomyocytes was compared with those of adult heart cells and hiPSC-derived cardiomyocytes from a previous report 41 ( Supplementary Fig. 10), the SOTR cardiomyocytes showed lower nodal-(TBX18, SHOX2, MSX2, TBX2, HCN1, HCN4) and atrial-related (MYH6, NPPA) and higher ventricular-related (MYL2) gene expression than the previously reported cardiomyocytes 41 . Both the SOTR cardiomyocytes and cardiomyocytes of the previous study showed lower expression of MYH7 and MYL2, but higher IRX4 expression than the adult cardiomyocytes.…”

Section: And 4)mentioning

confidence: 69%

Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

Zhang

et al. 2020

Commun Biol

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Directed differentiation methods allow acquisition of high-purity cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs); however, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes has been used for efficiently promoting the maturation of cardiomyocytes, here we describe a simple device in modified culture plate on which hiPSCderived cardiomyocytes can form three-dimensional self-organized tissue rings (SOTRs). Using calcium imaging, we show that within the ring, reentrant waves (ReWs) of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz. After 2 weeks, SOTRs with ReWs show higher maturation including structural organization, increased cardiac-specific gene expression, enhanced Ca 2+-handling properties, an increased oxygenconsumption rate, and enhanced contractile force. We subsequently use a mathematical model to interpret the origination, propagation, and long-term behavior of the ReWs within the SOTRs.

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Section: And 4)mentioning

confidence: 69%

Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

Zhang

et al. 2020

Commun Biol

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“…They show improved myofibrillar alignment and sarcolemma remodeling which led to better Ca 2+ handling (Silbernagel et al, 2020). Moreover, hiPSC-CMs in 3D culture exhibited faster maturation analyzed by transcriptome (Branco et al, 2019), while 2D cultures hinder the maturation or cause maturation arrest (Uosaki et al, 2015).…”

Section: General Concepts Of 3d Culturementioning

confidence: 99%

A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes

Ahmed¹,

Anzai²,

Chanthra³

et al. 2020

Front. Cell Dev. Biol.

170

154

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Cardiovascular diseases are the leading cause of death worldwide. Therefore, the discovery of induced pluripotent stem cells (iPSCs) and the subsequent generation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) was a pivotal point in regenerative medicine and cardiovascular research. They constituted an appealing tool for replacing dead and dysfunctional cardiac tissue, screening cardiac drugs and toxins, and studying inherited cardiac diseases. The problem is that these cells remain largely immature, and in order to utilize them, they must reach a functional degree of maturity. To attempt to mimic in vivo environment, various methods including prolonging culture time, co-culture and modulations of chemical, electrical, mechanical culture conditions have been tried. In addition to that, changing the topology of the culture made huge progress with the introduction of the 3D culture that closely resembles the in vivo cardiac topology and overcomes many of the limitations of the conventionally used 2D models. Nonetheless, 3D culture alone is not enough, and using a combination of these methods is being explored. In this review, we summarize the main differences between immature, fetal-like hiPSC-CMs and adult cardiomyocytes, then glance at the current approaches used to promote hiPSC-CMs maturation. In the second part, we focus on the evolving 3D culture model-it's structure, the effect on hiPSC-CMs maturation, incorporation with different maturation methods, limitations and future prospects.

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“…For instance, directed differentiation towards cardiomyocytes can be induced through the early activation of the Wnt pathway, which induces mesoderm differentiation. Accordingly, the 3D aggregation of human pluripotent stem cells was found to allow faster differentiation towards the cardiac lineage through the priming of mesodermal differentiation [ 36 ]. Moreover, EB size, the composition of different substrates, and mechanical cues can enhance the differentiation of EBs into specific lineages [ 37 , 38 , 39 ].…”

Section: Molecular Changes During Embryoid Body Formationmentioning

confidence: 99%

Cell Mechanics in Embryoid Bodies

Zeevaert

Mabrouk

Wagner

et al. 2020

Cells

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Embryoid bodies (EBs) resemble self-organizing aggregates of pluripotent stem cells that recapitulate some aspects of early embryogenesis. Within few days, the cells undergo a transition from rather homogeneous epithelial-like pluripotent stem cell colonies into a three-dimensional organization of various cell types with multifaceted cell–cell interactions and lumen formation—a process associated with repetitive epithelial-mesenchymal transitions. In the last few years, culture methods have further evolved to better control EB size, growth, cellular composition, and organization—e.g., by the addition of morphogens or different extracellular matrix molecules. There is a growing perception that the mechanical properties, cell mechanics, and cell signaling during EB development are also influenced by physical cues to better guide lineage specification; substrate elasticity and topography are relevant, as well as shear stress and mechanical strain. Epithelial structures outside and inside EBs support the integrity of the cell aggregates and counteract mechanical stress. Furthermore, hydrogels can be used to better control the organization and lineage-specific differentiation of EBs. In this review, we summarize how EB formation is accompanied by a variety of biomechanical parameters that need to be considered for the directed and reproducible self-organization of early cell fate decisions.

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Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture

Cited by 91 publications

References 59 publications

Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

Circulating re-entrant waves promote maturation of hiPSC-derived cardiomyocytes in self-organized tissue ring

A Brief Review of Current Maturation Methods for Human Induced Pluripotent Stem Cells-Derived Cardiomyocytes

Cell Mechanics in Embryoid Bodies

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