The Role of Reactive Oxygen Species in In Vitro Cardiac Maturation

Momtahan, Nima; Crosby, Cody; Zoldan, Janet

doi:10.1016/j.molmed.2019.04.005

Cited by 19 publications

(19 citation statements)

References 96 publications

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“…Maintaining mitophagy may inhibit senescence and promote cardiomyocyte maturation. [202]. At physiologic levels, oxidation of selected proteins can maintain normal cellular function, but in excess, nonspecific oxidation of cellular contents can be toxic [203].…”

Section: Mitophagymentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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Current methods to differentiate cardiomyocytes from human pluripotent stem cells (PSCs) inadequately recapitulate complete development and result in PSC-derived cardiomyocytes (PSC-CMs) with an immature or fetal-like phenotype. Embryonic and fetal development are highly dynamic periods during which the developing embryo or fetus is exposed to changing nutrient, oxygen, and hormone levels until birth. It is becoming increasingly apparent that these metabolic changes initiate developmental processes to mature cardiomyocytes. Mitochondria are central to these changes, responding to these metabolic changes and transitioning from small, fragmented mitochondria to large organelles capable of producing enough ATP to support the contractile function of the heart. These changes in mitochondria may not simply be a response to cardiomyocyte maturation; the metabolic signals that occur throughout development may actually be central to the maturation process in cardiomyocytes. Here, we review methods to enhance maturation of PSC-CMs and highlight evidence from development indicating the key roles that mitochondria play during cardiomyocyte maturation. We evaluate metabolic transitions that occur during development and how these affect molecular nutrient sensors, discuss how regulation of nutrient sensing pathways affect mitochondrial dynamics and function, and explore how changes in mitochondrial function can affect metabolite production, the cell cycle, and epigenetics to influence maturation of cardiomyocytes.

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Section: Mitophagymentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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“…The limit between a beneficial and deleterious response (oxidative eustress and distress, respectively) remains to be clearly evaluated in health and disease [183]. Evidence shows that normal levels of ROS play a critical role in cellular homeostasis and function during the cardiovascular commitment [188][189][190]. Indeed, Li and colleagues showed a link between H 2 O 2 treatment and the gene expression of cardiogenesis, demonstrating that ROS signals are indispensable in modifying cell fates through the induction of cardiac-specific genes such as GATA4, NKX2-5 and MEF2C [184].…”

Section: The Role Of Hypoxia and Reactive Oxygen Species On Cardiomyocytesmentioning

confidence: 99%

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

Lamberto

Peral-Sanchez

Muenthaisong

et al. 2021

Genes

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Non-communicable diseases (NCDs) sauch as diabetes, obesity and cardiovascular diseases are rising rapidly in all countries world-wide. Environmental maternal factors (e.g., diet, oxidative stress, drugs and many others), maternal illnesses and other stressors can predispose the newborn to develop diseases during different stages of life. The connection between environmental factors and NCDs was formulated by David Barker and colleagues as the Developmental Origins of Health and Disease (DOHaD) hypothesis. In this review, we describe the DOHaD concept and the effects of several environmental stressors on the health of the progeny, providing both animal and human evidence. We focus on cardiovascular diseases which represent the leading cause of death worldwide. The purpose of this review is to discuss how in vitro studies with pluripotent stem cells (PSCs), such as embryonic and induced pluripotent stem cells (ESC, iPSC), can underpin the research on non-genetic heart conditions. The PSCs could provide a tool to recapitulate aspects of embryonic development “in a dish”, studying the effects of environmental exposure during cardiomyocyte (CM) differentiation and maturation, establishing a link to molecular mechanism and epigenetics.

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“…Clinical application of stem cell therapies requires large-scale cell culture technologies such as bioreactors that allow for conditional manipulations of the survival, differentiation, and maturation of PSC-CMs [125]. Maintenance of low cellular H 2 O 2 concentration may facilitate in vitro maturation of PSC-CMs [126]. However, PSC-CMs appear to be particularly sensitive to hypoxia and nutrient deprivation-induced cell death associated with increased ROS formation and modulation of key nutrient sensors [127].…”

Section: A High Level Of Intracellular or Extracellular Ros Harmsmentioning

confidence: 99%

Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies

Liang

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Reactive oxygen species (ROS) have been implicated in mechanisms of heart development and regenerative therapies such as the use of pluripotent stem cells. The roles of ROS mediating cell fate are dependent on the intensity of stimuli, cellular context, and metabolic status. ROS mainly act through several targets (such as kinases and transcription factors) and have diverse roles in different stages of cardiac differentiation, proliferation, and maturation. Therefore, further detailed investigation and characterization of redox signaling will help the understanding of the molecular mechanisms of ROS during different cellular processes and enable the design of targeted strategies to foster cardiac regeneration and functional recovery. In this review, we focus on the roles of ROS in cardiac differentiation as well as transdifferentiation (direct reprogramming). The potential mechanisms are discussed in regard to ROS generation pathways and regulation of downstream targets. Further methodological optimization is required for translational research in order to robustly enhance the generation efficiency of cardiac myocytes through metabolic modulations. Additionally, we highlight the deleterious effect of the host’s ROS on graft (donor) cells in a paracrine manner during stem cell-based implantation. This knowledge is important for the development of antioxidant strategies to enhance cell survival and engraftment of tissue engineering-based technologies. Thus, proper timing and level of ROS generation after a myocardial injury need to be tailored to ensure the maximal efficacy of regenerative therapies and avoid undesired damage.

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The Role of Reactive Oxygen Species in In Vitro Cardiac Maturation

Cited by 19 publications

References 96 publications

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

Roles of Reactive Oxygen Species in Cardiac Differentiation, Reprogramming, and Regenerative Therapies

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