Full-length dystrophin deficiency leads to contractile and calcium transient defects in human engineered heart tissues

Bremner, Samantha; Mandrycky, Christian; Leonard, Andrea; Levinson, Alan R.; Rehn, Ethan S.; Pioner, JM; Sniadecki, Nathan J.; Mack, David L.

doi:10.1016/j.bpj.2021.11.652

Cited by 1 publication

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“…Bremner and coauthors [83] used hiPSC-CMs in the form of engineered heart tissues (EHTs) that provide a 3D physiological cell culture platform to faithfully mimic mature cardiac tissue structure [84][85][86]. Contrary to a 2D culture, comparison of DMD and healthy EHT cardiomyocytes demonstrated dysregulation of genes related to cardiac function, including many related to cardiac muscle development, action potential and contraction, as well as extracellular matrix organization in DMD cardiomyocytes.…”

Section: Gene Expression Changes In Dmd Hipsc-cmsmentioning

confidence: 99%

“…Bremner and coauthors [83] measured contractile force in electrically stimulated hiPSC-CMs 3D EHT to mimic mature cardiac tissue structure [84][85][86]. DMD cardiomyocytes generated decreased twitch force and contraction kinetic parameters compared to healthy cardiomyocytes, implying lower contractile performance.…”

Section: Abnormal Excitation-contraction Coupling Machinery In Dmd Hi...mentioning

confidence: 99%

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Modeling Duchenne Muscular Dystrophy Cardiomyopathy with Patients’ Induced Pluripotent Stem-Cell-Derived Cardiomyocytes

Eisen

Binah

2023

IJMS

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Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative disease caused by mutations in the dystrophin gene, resulting in death by the end of the third decade of life at the latest. A key aspect of the DMD clinical phenotype is dilated cardiomyopathy, affecting virtually all patients by the end of the second decade of life. Furthermore, despite respiratory complications still being the leading cause of death, with advancements in medical care in recent years, cardiac involvement has become an increasing cause of mortality. Over the years, extensive research has been conducted using different DMD animal models, including the mdx mouse. While these models present certain important similarities to human DMD patients, they also have some differences which pose a challenge to researchers. The development of somatic cell reprograming technology has enabled generation of human induced pluripotent stem cells (hiPSCs) which can be differentiated into different cell types. This technology provides a potentially endless pool of human cells for research. Furthermore, hiPSCs can be generated from patients, thus providing patient-specific cells and enabling research tailored to different mutations. DMD cardiac involvement has been shown in animal models to include changes in gene expression of different proteins, abnormal cellular Ca2+ handling, and other aberrations. To gain a better understanding of the disease mechanisms, it is imperative to validate these findings in human cells. Furthermore, with the recent advancements in gene-editing technology, hiPSCs provide a valuable platform for research and development of new therapies including the possibility of regenerative medicine. In this article, we review the DMD cardiac-related research performed so far using human hiPSCs-derived cardiomyocytes (hiPSC-CMs) carrying DMD mutations.

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Section: Gene Expression Changes In Dmd Hipsc-cmsmentioning

confidence: 99%

Section: Abnormal Excitation-contraction Coupling Machinery In Dmd Hi...mentioning

confidence: 99%

Modeling Duchenne Muscular Dystrophy Cardiomyopathy with Patients’ Induced Pluripotent Stem-Cell-Derived Cardiomyocytes

Eisen

Binah

2023

IJMS

View full text Add to dashboard Cite

show abstract

Full-length dystrophin deficiency leads to contractile and calcium transient defects in human engineered heart tissues

Cited by 1 publication

References 65 publications

Modeling Duchenne Muscular Dystrophy Cardiomyopathy with Patients’ Induced Pluripotent Stem-Cell-Derived Cardiomyocytes

Modeling Duchenne Muscular Dystrophy Cardiomyopathy with Patients’ Induced Pluripotent Stem-Cell-Derived Cardiomyocytes

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