Human Induced Pluripotent Stem Cells Derived from a Cardiac Somatic Source: Insights for an In-Vitro Cardiomyocyte Platform

Lodrini, Alessandra Maria; Barile, Lucio; Rocchetti, Marcella; Altomare, Claudia

doi:10.3390/ijms21020507

Cited by 15 publications

(10 citation statements)

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“…Cardiomyocytes (CM) derived from human induced pluripotent stem cells (hiPSC) are mainly characterised by a heterogeneous mixture of immature ventricular-, atrial- and nodal-like CM phenotypes whose proportion depends on differentiation timing and protocols 1 . This aspect affects the identification and characterisation of electrical properties of hiPSC-CM subtypes, which is crucial in studies investigating chamber-specific disease mechanisms or addressing potential drug-induced cardiotoxicity during the development of pharmaceutical molecules 2 .…”

Section: Introductionmentioning

confidence: 99%

A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes

et al. 2023

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Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) constitute a mixed population of ventricular-, atrial-, nodal-like cells, limiting the reliability for studying chamber-specific disease mechanisms. Previous studies characterised CM phenotype based on action potential (AP) morphology, but the classification criteria were still undefined. Our aim was to use in silico models to develop an automated approach for discriminating the electrophysiological differences between hiPSC-CM. We propose the dynamic clamp (DC) technique with the injection of a specific IK1 current as a tool for deriving nine electrical biomarkers and blindly classifying differentiated CM. An unsupervised learning algorithm was applied to discriminate CM phenotypes and principal component analysis was used to visualise cell clustering. Pharmacological validation was performed by specific ion channel blocker and receptor agonist. The proposed approach improves the translational relevance of the hiPSC-CM model for studying mechanisms underlying inherited or acquired atrial arrhythmias in human CM, and for screening anti-arrhythmic agents.

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Section: Introductionmentioning

confidence: 99%

A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes

et al. 2023

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“…The protocols for differentiation can be complex and require optimization for each cell type, and there can be significant variability in the quality and purity of the differentiated cells produced. Additionally, there may be functional differences between iPSC-derived cells and their natural counterparts, which may limit their therapeutic potential [ 70 , 71 , 72 , 73 , 74 ].…”

Section: Ipscsmentioning

confidence: 99%

Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems

Silva-Pedrosa

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Ferreira

2023

Cells

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Cellular models have created opportunities to explore the characteristics of human diseases through well-established protocols, while avoiding the ethical restrictions associated with post-mortem studies and the costs associated with researching animal models. The capability of cell reprogramming, such as induced pluripotent stem cells (iPSCs) technology, solved the complications associated with human embryonic stem cells (hESC) usage. Moreover, iPSCs made significant contributions for human medicine, such as in diagnosis, therapeutic and regenerative medicine. The two-dimensional (2D) models allowed for monolayer cellular culture in vitro; however, they were surpassed by the three-dimensional (3D) cell culture system. The 3D cell culture provides higher cell–cell contact and a multi-layered cell culture, which more closely respects cellular morphology and polarity. It is more tightly able to resemble conditions in vivo and a closer approach to the architecture of human tissues, such as human organoids. Organoids are 3D cellular structures that mimic the architecture and function of native tissues. They are generated in vitro from stem cells or differentiated cells, such as epithelial or neural cells, and are used to study organ development, disease modeling, and drug discovery. Organoids have become a powerful tool for understanding the cellular and molecular mechanisms underlying human physiology, providing new insights into the pathogenesis of cancer, metabolic diseases, and brain disorders. Although organoid technology is up-and-coming, it also has some limitations that require improvements.

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“…For example, the reprogramming process and the maturation of reprogrammed cells (in terms of cellular size, structural and morphological traits, electrophysiological properties, and metabolic profile) in order to effectively resemble to adult native myocytes and recapitulate molecular and functional aspects of human heart disease phenotypes takes several months and requires a substantial investment of labor. [ 64 ] Furthermore, cardiomyocyte is not always the direct target of toxicity; immune checkpoint inhibitors (ICIs) elicit their antitumor response by targeting inhibitory receptors (e.g., CTLA‐4, PD‐1, LAG‐3, TIM‐3) and ligands (PD‐L1) expressed on T lymphocytes, antigen presenting cells and tumor cells. [ 65 ] In this respect, in patients receiving ICIs, cardiovascular adverse events (i.e., myocarditis) are immune‐related; possible mechanisms include i) direct binding to cell surface proteins expressed in nonlymphocytic cells, ii) activation of T cells that cross‐react with off‐target tissues, iii) generation of autoantibodies and production of proinflammatory cytokines.…”

Section: Future Perspectives: Reshaping Our Strategy Based On New Tec...mentioning

confidence: 99%

Molecular biomarkers in cardio‐oncology: Where we stand and where we are heading

2022

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Until recently, cardiotoxicity in the setting of a malignant disease was attributed solely to the detrimental effects of chemo-and/or radio-therapy to the heart. On this account, the focus was on the evaluation of well-established cardiac biomarkers for the early detection of myocardial damage. Currently, this view has been revised. Cardiotoxicity is not restricted to a single organ but instead affects the endothelium as a whole.Indeed, it has come into light that not only cancer therapy but also malignant cells per se can impair the cardiovascular system, through a paracrine and endocrine mode of action. Even more intriguingly, a clear interplay between molecular pathways involved in cancer and cardiovascular disease has become prevalent, suggesting a common nominator that governs the pathophysiology of these two entities. Taken together, our strategy in the quest of novel biomarkers in the emerging field of cardio-oncology should be critically reshaped.

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Human Induced Pluripotent Stem Cells Derived from a Cardiac Somatic Source: Insights for an In-Vitro Cardiomyocyte Platform

Cited by 15 publications

References 145 publications

A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes

A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes

Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems

Molecular biomarkers in cardio‐oncology: Where we stand and where we are heading

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