Enhancing iPSC‐CM Maturation Using a Matrigel‐Coated Micropatterned PDMS Substrate

Jiménez-Vázquez, Eric N.; Jain, Abhilasha; Jones, David K.

doi:10.1002/cpz1.601

“…The iPSC‐CM acquired rod shape morphology and mature contractile function, calcium handling, and electrophysiology. [ 115 ] As discussed, multiple biochemical and topographical strategies have been implemented for the enhanced maturation of iPSC‐CM. ( Figure ) A recent strategy used to fabricate cardiac tissue constructs is layering.…”

Section: Closing the Gap In Hipsc‐cms Maturitymentioning

confidence: 99%

Advancing Cardiomyocyte Maturation: Current Strategies and Promising Conductive Polymer‐Based Approaches

Elkhoury,

Kodeih,

Enciso‐Martínez

et al. 2024

Adv Healthcare Materials

0

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Cardiovascular diseases are a leading cause of mortality and pose a significant burden on healthcare systems worldwide. Despite remarkable progress in medical research, the development of effective cardiovascular drugs has been hindered by high failure rates and escalating costs. One contributing factor is the limited availability of mature cardiomyocytes (CMs) for accurate disease modeling and drug screening. Human induced pluripotent stem cell‐derived CMs offer a promising source of CMs; however, their immature phenotype presents challenges in translational applications. This review focuses on the road to achieving mature CMs by summarizing the major differences between immature and mature CMs, discussing the importance of adult‐like CMs for drug discovery, highlighting the limitations of current strategies, and exploring potential solutions using electro‐mechano active polymer‐based scaffolds based on conductive polymers. However, critical considerations such as the trade‐off between three‐dimensional systems and nutrient exchange, biocompatibility, degradation, cell adhesion, longevity, and integration into wider systems must be carefully evaluated. Continued advancements in these areas will contribute to a better understanding of cardiac diseases, improved drug discovery, and the development of personalized treatment strategies for patients with cardiovascular disorders.This article is protected by copyright. All rights reserved

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“…Accordingly, innovative maturation strategies were developed to increase the maturity of the cells produced. Current methods include: micropatterning, metabolic maturation, electrical stimulation, soft-substrate culture, co-culture, and engineered 3D models (Jimenez-Vazquez et al, 2022;Feyen et al, 2020;Yoshida et al, 2018;Tzatzalos et al, 2016;Machiraju and Greenway, 2019).…”

Section: Revised Amendments From Versionmentioning

confidence: 99%

Generation of a human iPSC-derived cardiomyocyte/fibroblast engineered heart tissue model

Cumberland,

Euchner,

Azad

et al. 2023

F1000Res

0

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Animal models have proven integral to broadening our understanding of complex cardiac diseases but have been hampered by significant species-dependent differences in cellular physiology. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have shown great promise in the modelling of cardiac diseases despite limitations in functional and structural maturity. 3D stem cell-derived cardiac models represent a step towards mimicking the intricate microenvironment present in the heart as an in vitro model. Incorporation of non-myocyte cell types, such as cardiac fibroblasts, into engineered heart tissue models (EHTs) can help better recapitulate the cell-to-cell and cell-to-matrix interactions present in the human myocardium. Integration of human-induced pluripotent stem cell-derived cardiac fibroblasts (hiPSC-CFs) and hiPSC-CM into EHT models enables the generation of a genetically homogeneous modelling system capable of exploring the abstruse structural and electrophysiological interplay present in cardiac pathophysiology. Furthermore, the construction of more physiologically relevant 3D cardiac models offers great potential in the replacement of animals in heart disease research. Here we describe efficient and reproducible protocols for the differentiation of hiPSC-CMs and hiPSC-CFs and their subsequent assimilation into EHTs. The resultant EHT consists of longitudinally arranged iPSC-CMs, incorporated alongside hiPSC-CFs. EHTs with both hiPSC-CMs and hiPSC-CFs exhibit slower beating frequencies and enhanced contractile force compared to those composed of hiPSC-CMs alone. The modified protocol may help better characterise the interplay between different cell types in the myocardium and their contribution to structural remodelling and cardiac fibrosis.

show abstract

“…Accordingly, innovative maturation strategies were developed to increase the maturity of the cells produced. Current methods include: micropatterning, metabolic maturation, electrical stimulation, soft-substrate culture, co-culture, and engineered 3D models ( Jimenez-Vazquez et al ., 2022 ; Feyen et al ., 2020 ; Yoshida et al ., 2018 ; Tzatzalos et al ., 2016 ; Machiraju and Greenway, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Generation of a human iPSC-derived cardiomyocyte/fibroblast engineered heart tissue model

Cumberland,

Euchner,

Azad

et al. 2024

F1000Res

0

View full text Add to dashboard Cite

Animal models have proven integral to broadening our understanding of complex cardiac diseases but have been hampered by significant species-dependent differences in cellular physiology. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have shown great promise in the modelling of cardiac diseases despite limitations in functional and structural maturity. 3D stem cell-derived cardiac models represent a step towards mimicking the intricate microenvironment present in the heart as an in vitro model. Incorporation of non-myocyte cell types, such as cardiac fibroblasts, into engineered heart tissue models (EHTs) can help better recapitulate the cell-to-cell and cell-to-matrix interactions present in the human myocardium. Integration of human-induced pluripotent stem cell-derived cardiac fibroblasts (hiPSC-CFs) and hiPSC-CM into EHT models enables the generation of a genetically homogeneous modelling system capable of exploring the abstruse structural and electrophysiological interplay present in cardiac pathophysiology. Furthermore, the construction of more physiologically relevant 3D cardiac models offers great potential in the replacement of animals in heart disease research. Here we describe efficient and reproducible protocols for the differentiation of hiPSC-CMs and hiPSC-CFs and their subsequent assimilation into EHTs. The resultant EHT consists of longitudinally arranged iPSC-CMs, incorporated alongside hiPSC-CFs. EHTs with both hiPSC-CMs and hiPSC-CFs exhibit slower beating frequencies and enhanced contractile force compared to those composed of hiPSC-CMs alone. The modified protocol may help better characterise the interplay between different cell types in the myocardium and their contribution to structural remodelling and cardiac fibrosis.

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Enhancing iPSC‐CM Maturation Using a Matrigel‐Coated Micropatterned PDMS Substrate

Cited by 5 publications

References 66 publications

Advancing Cardiomyocyte Maturation: Current Strategies and Promising Conductive Polymer‐Based Approaches

Advancing Cardiomyocyte Maturation: Current Strategies and Promising Conductive Polymer‐Based Approaches

Generation of a human iPSC-derived cardiomyocyte/fibroblast engineered heart tissue model

Generation of a human iPSC-derived cardiomyocyte/fibroblast engineered heart tissue model

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