Cellular models for human cardiomyopathy: What is the best option?

Jimenez-Tellez, Nerea; Greenway, Steven C.

doi:10.4330/wjc.v11.i10.221

Cited by 18 publications

(13 citation statements)

References 130 publications

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“…There is thus a need for models that can recapitulate key features observed in human cardiomyopathies and can be used for disease modeling and therapeutic testing. Animal models are the most common models for cardiomyopathies [ 13 ] but have inherent limitations to recapitulate complex human physiopathology as well as inter-patient genetic variability [ 14 , 15 ]. For these reasons, the translation of targeted therapies for cardiomyopathies from animal trials to human subjects has been limited so far.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

et al. 2021

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Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

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Section: Introductionmentioning

confidence: 99%

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

et al. 2021

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“…In this context, iPSCs offer unprecedented opportunities since these cells can be directed to become any cell type in the body [ 15 ]. iPSC-derived cardiomyocytes (iPSC-CMs) represent a good cellular model in which disease mechanisms can be experimentally deciphered in a human context [ 16 ]. A significant number of PA patients develop cardiac complications, and available evidence suggests that this cardiac dysfunction is mainly driven by the accumulation of toxic metabolites [ 2 , 3 , 17 , 18 ].…”

Section: Resultsmentioning

confidence: 99%

Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia

Alonso-Barroso

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Desviat

et al. 2021

IJMS

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Propionic acidemia (PA), one of the most frequent life-threatening organic acidemias, is caused by mutations in either the PCCA or PCCB genes encoding both subunits of the mitochondrial propionyl-CoA carboxylase (PCC) enzyme. Cardiac alterations (hypertrophy, dilated cardiomyopathy, long QT) are one of the major causes of mortality in patients surviving the neonatal period. To overcome limitations of current cellular models of PA, we generated induced pluripotent stem cells (iPSCs) from a PA patient with defects in the PCCA gene, and successfully differentiated them into cardiomyocytes. PCCA iPSC-derived cardiomyocytes exhibited reduced oxygen consumption, an accumulation of residual bodies and lipid droplets, and increased ribosomal biogenesis. Furthermore, we found increased protein levels of HERP, GRP78, GRP75, SIG-1R and MFN2, suggesting endoplasmic reticulum stress and calcium perturbations in these cells. We also analyzed a series of heart-enriched miRNAs previously found deregulated in the heart tissue of a PA murine model and confirmed their altered expression. Our novel results show that PA iPSC-cardiomyocytes represent a promising model for investigating the pathological mechanisms underlying PA cardiomyopathies, also serving as an ex vivo platform for therapeutic evaluation.

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“…Taken together, the previous reports provide substantial information on how to model several outcomes that account for the cardiac deterioration observed in many COVID-19 patients. Studies that use patient-derived hiPSC-CMs carrying inherited diseases can also be found in the literature ( Granéli et al, 2019 ; Hoes et al, 2019 ; Jimenez-Tellez and Greenway, 2019 ). Several of these models can be adopted to evaluate additive effects of COVID-19 and pre-existing comorbidities such as heart failure, cardiomyopathies, diabetes.…”

Section: Modeling the “Covid-19 Cardiomyocyte” In Vitromentioning

confidence: 99%

In vitro and In silico Models to Study SARS-CoV-2 Infection: Integrating Experimental and Computational Tools to Mimic “COVID-19 Cardiomyocyte”

et al. 2021

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The rapid dissemination of SARS-CoV-2 has made COVID-19 a tremendous social, economic, and health burden. Despite the efforts to understand the virus and treat the disease, many questions remain unanswered about COVID-19 mechanisms of infection and progression. Severe Acute Respiratory Syndrome (SARS) infection can affect several organs in the body including the heart, which can result in thromboembolism, myocardial injury, acute coronary syndromes, and arrhythmias. Numerous cardiac adverse events, from cardiomyocyte death to secondary effects caused by exaggerated immunological response against the virus, have been clinically reported. In addition to the disease itself, repurposing of treatments by using “off label” drugs can also contribute to cardiotoxicity. Over the past several decades, animal models and more recently, stem cell-derived cardiomyocytes have been proposed for studying diseases and testing treatments in vitro. In addition, mechanistic in silico models have been widely used for disease and drug studies. In these models, several characteristics such as gender, electrolyte imbalance, and comorbidities can be implemented to study pathophysiology of cardiac diseases and to predict cardiotoxicity of drug treatments. In this Mini Review, we (1) present the state of the art of in vitro and in silico cardiomyocyte modeling currently in use to study COVID-19, (2) review in vitro and in silico models that can be adopted to mimic the effects of SARS-CoV-2 infection on cardiac function, and (3) provide a perspective on how to combine some of these models to mimic “COVID-19 cardiomyocytes environment.”

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Cellular models for human cardiomyopathy: What is the best option?

Cited by 18 publications

References 130 publications

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia

In vitro and In silico Models to Study SARS-CoV-2 Infection: Integrating Experimental and Computational Tools to Mimic “COVID-19 Cardiomyocyte”

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