Unique Metabolic Features of Stem Cells, Cardiomyocytes, and Their Progenitors

Gaspar, John Antonydas; Doss, Michael Xavier; Hengstler, Jan G.; Cadenas, Cristina; Hescheler, Juergen; Sachinidis, Agapios

doi:10.1161/circresaha.113.302021

Cited by 77 publications

(71 citation statements)

References 137 publications

(205 reference statements)

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“…Differentiation of cells is associated with a large increase in energy demand (55), and our data demonstrate that there is an increase in proteins involved in OXPHOS and a corresponding decrease in enzymes involved in cytosolic glycolysis in CPCs. The most surprising finding in our study is that the POLG CPCs rely solely on glycolysis for energy production instead of mitochondrial respiration.…”

Section: Discussionsupporting

confidence: 51%

Accumulation of Mitochondrial DNA Mutations Disrupts Cardiac Progenitor Cell Function and Reduces Survival

Orogo

Gonzalez

Kubli

et al. 2015

Journal of Biological Chemistry

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Background: Mitochondrial DNA (mtDNA) mutations accumulate with age, but how this impacts cardiac progenitor cell (CPC) function is unknown. Results: mtDNA mutations disrupt mitochondrial function and reduce differentiation potential of CPCs. Conclusion: Preserving mtDNA integrity is critical for CPC homeostasis and regenerative potential. Significance: Increased understanding of pathways regulating progenitor cell function is critical for development of effective cell therapies.

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Section: Discussionsupporting

confidence: 51%

Accumulation of Mitochondrial DNA Mutations Disrupts Cardiac Progenitor Cell Function and Reduces Survival

Orogo

Gonzalez

Kubli

et al. 2015

Journal of Biological Chemistry

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“…Due to their small size the terminated embryos are not often studied in detail, but where reported, they seem to lack all heart structures [52]. This fits well to the fact that also cardiomyocyte differentiation in vitro requires functional OXPHOS [53]. Therefore it is rather surprising that although the embryonic heart is perfectly capable of oxidative metabolism, it has been thought to rely on anaerobic glycolysis [3].…”

Section: Mitochondrial Function Is Essential For Heart Developmentmentioning

confidence: 99%

The role of mitochondria in cardiac development and protection

Pohjoismäki

Goffart

2017

Free Radical Biology and Medicine

101

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Mitochondria are essential for the development as well as maintenance of the myocardium, the most energy consuming tissue in the human body. Mitochondria are not only a source of ATP energy but also generators of reactive oxygen species (ROS), that cause oxidative damage, but also regulate physiological processes such as the switch from hyperplastic to hypertrophic growth after birth. As excess ROS production and oxidative damage are associated with cardiac pathology, it is not surprising that much of the research focused on the deleterious aspects of free radicals. However, cardiomyocytes are naturally highly adapted against repeating oxidative insults, with evidence suggesting that moderate and acute ROS exposure has beneficial consequences for mitochondrial maintenance and cardiac health. Antioxidant defenses, mitochondrial quality control, mtDNA maintenance mechanisms as well as mitochondrial fusion and fission improve mitochondrial function and cardiomyocyte survival under stress conditions. As these adaptive processes can be induced, promoting mitohormesis or mitochondrial biogenesis using controlled ROS exposure could provide a promising strategy to increase cardiomyocyte survival and prevent pathological remodeling of the myocardium.

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“…Recent studies suggest that iPSC-cardiomyocytes can reveal cardiotoxicities manifesting as alterations in cardiomyocyte viability, contractility, intracellular signaling and gene expression [127, 128]. As above, however, there is great need for validation, especially considering that many anti-cancer drugs elicit their cardiac effects by affecting mitochondrial function [129, 130] and that iPSC-cardiomyocytes are metabolically immature [131]. Furthermore, it will be important to evaluate the influence that patient-to-patient variation has on drug effects, as well as differences in production and culture protocols on anti-cancer drug effects is largely unexplored.…”

Section: Modeling Cardiotoxicitymentioning

confidence: 99%

High throughput physiological screening of iPSC-derived cardiomyocytes for drug development

Álamo

Lemons

Serrano

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

105

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Cardiac drug discovery is hampered by the reliance on non-human animal and cellular models with inadequate throughput and physiological fidelity to accurately identify new targets and test novel therapeutic strategies. Similarly, adverse drug effects on the heart are challenging to model, contributing to costly failure of drugs during development and even after market launch. Human induced pluripotent stem cell derived cardiac tissue represents a potentially powerful means to model aspects of heart physiology relevant to disease and adverse drug effects, providing both the human context and throughput needed to improve the efficiency of drug development. Here we review emerging technologies for high throughput measurements of cardiomyocyte physiology, and comment on the promises and challenges of using iPSC-derived cardiomyocytes to model disease and introduce the human context into early stages of drug discovery.

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Unique Metabolic Features of Stem Cells, Cardiomyocytes, and Their Progenitors

Abstract: phorylation (OXPHOS). 2,3 ATP can also be generated by the degradation of lipids, including triglycerides and phospholipids into fatty acids, which are metabolized in the mitochondria

Cited by 77 publications

References 137 publications

Accumulation of Mitochondrial DNA Mutations Disrupts Cardiac Progenitor Cell Function and Reduces Survival

Accumulation of Mitochondrial DNA Mutations Disrupts Cardiac Progenitor Cell Function and Reduces Survival

The role of mitochondria in cardiac development and protection

High throughput physiological screening of iPSC-derived cardiomyocytes for drug development

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