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Metabolites
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The Studies of Metabolic Changes in Cardiac Stem Cells Differentiation
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The Studies of Metabolic Changes in Cardiac Stem Cells Differentiation

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 11337

Special Issue Editor

Prof. Dr. Carolyn A. Carr

E-Mail Website
Guest Editor
Department of Physiology, Anatomy, and Genetics,Sherrington Building, University of Oxford, Oxford OX1 3PT, UK
Interests: cardiac physiology and metabolism; endogenous cardiac stem cells to prevent heart failure; MR spectroscopy and mass spectrometry; metabolic changes in stem cells as they differentiate

Special Issue Information

Dear Colleagues,

The development of techniques to differentiate pluripotent stem cells into heart cells and keep them in the lab for many weeks has opened up the possibility of testing the effect of drugs or of genetic disorders on the heart in human cardiomyocytes. However, pluripotent stem cell-derived cardiomyocytes are immature and have not developed all the proteins and signaling pathways of the adult heart. A range of techniques have been used to induce maturation of stem cell-derived cardiomyocytes so that they fully recapitulate the phenotype of the adult heart, including genetic approaches, mechanical and/or electrical stimulation, 3D culture and modification of the cell culture medium. Only recently have the induction of metabolic changes and their measurement been taken into consideration.

This special issue of Metabolites will be dedicated to studies which focus on metabolic changes in differentiating cardiomyocytes, both those from pluripotent stem cells and from endogenous progenitors, Both research articles and reviews are welcome and topics can include the use of metabolic stimuli to induce maturation; the characterization of metabolic changes during differentiation; modelling metabolic disorders in vitro and techniques to characterize metabolism in stem-cell derived cardiomyocytes.

Dr. Carolyn A. Carr
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (3 papers)

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Research

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16 pages, 2593 KiB  
Article
Metabolic Remodeling during Early Cardiac Lineage Specification of Pluripotent Stem Cells
by Sunday Ndoma Bobori, Yuxiang Zhu, Alicia Saarinen, Alexis Josephine Liuzzo and Clifford D. L. Folmes
Metabolites 2023, 13(10), 1086; https://doi.org/10.3390/metabo13101086 - 17 Oct 2023
Cited by 1 | Viewed by 2128
Abstract
Growing evidence indicates that metabolites and energy metabolism play an active rather than consequential role in regulating cellular fate. Cardiac development requires dramatic metabolic remodeling from relying primarily on glycolysis in pluripotent stem cells (PSCs) to oxidizing a wide array of energy substrates [...] Read more.
Growing evidence indicates that metabolites and energy metabolism play an active rather than consequential role in regulating cellular fate. Cardiac development requires dramatic metabolic remodeling from relying primarily on glycolysis in pluripotent stem cells (PSCs) to oxidizing a wide array of energy substrates to match the high bioenergetic demands of continuous contraction in the developed heart. However, a detailed analysis of how remodeling of energy metabolism contributes to human cardiac development is lacking. Using dynamic multiple reaction monitoring metabolomics of central carbon metabolism, we evaluated temporal changes in energy metabolism during human PSC 3D cardiac lineage specification. Significant metabolic remodeling occurs during the complete differentiation, yet temporal analysis revealed that most changes occur during transitions from pluripotency to mesoderm (day 1) and mesoderm to early cardiac (day 5), with limited maturation of cardiac metabolism beyond day 5. Real-time metabolic analysis demonstrated that while hPSC cardiomyocytes (hPSC-CM) showed elevated rates of oxidative metabolism compared to PSCs, they still retained high glycolytic rates, confirming an immature metabolic phenotype. These observations support the opportunity to metabolically optimize the differentiation process to support lineage specification and maturation of hPSC-CMs. Full article
(This article belongs to the Special Issue The Studies of Metabolic Changes in Cardiac Stem Cells Differentiation)
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20 pages, 4049 KiB  
Article
Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells
by Benjamin B. Johnson, Johannes Reinhold, Terri L. Holmes, Jamie A. Moore, Verity Cowell, Andreia S. Bernardo, Stuart A. Rushworth, Vassilios Vassiliou and James G. W. Smith
Metabolites 2022, 12(1), 9; https://doi.org/10.3390/metabo12010009 - 22 Dec 2021
Cited by 7 | Viewed by 4586
Abstract
Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During heart development, metabolism matures and shifts from the predominant utilisation of glycolysis and glutamine oxidation towards lactate and fatty acid oxidation. Iron deficiency (ID) leads to cellular metabolism [...] Read more.
Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During heart development, metabolism matures and shifts from the predominant utilisation of glycolysis and glutamine oxidation towards lactate and fatty acid oxidation. Iron deficiency (ID) leads to cellular metabolism perturbations. However, the exact alterations in substrate metabolism during ID are poorly defined. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), the present study investigated changes in major metabolic substrate utilisation in the context of ID or upon transferrin rescue. Typically, during hiPSC-CM differentiation, the greatest increase in total metabolic output and rate was seen in fatty acid metabolism. When ID was induced, hiPSC-CMs displayed increased reliance on glycolytic metabolism, and six TCA cycle, five amino acid, and four fatty acid substrates were significantly impaired. Transferrin rescue was able to improve TCA cycle substrate metabolism, but the amino acid and fatty acid metabolism remained perturbed. Replenishing iron stores partially reverses the adverse metabolic changes that occur during ID. Understanding the changes in metabolic substrate utilisation and their modification may provide potential for discovery of new biomarkers and therapeutic targets in cardiovascular diseases. Full article
(This article belongs to the Special Issue The Studies of Metabolic Changes in Cardiac Stem Cells Differentiation)
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Review

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14 pages, 1088 KiB  
Review
Modelling Diabetic Cardiomyopathy: Using Human Stem Cell-Derived Cardiomyocytes to Complement Animal Models
by Ujang Purnama, Marcos Castro-Guarda, Om Saswat Sahoo and Carolyn A. Carr
Metabolites 2022, 12(9), 832; https://doi.org/10.3390/metabo12090832 - 3 Sep 2022
Cited by 5 | Viewed by 3852
Abstract
Diabetes is a global epidemic, with cardiovascular disease being the leading cause of death in diabetic patients. There is a pressing need for an in vitro model to aid understanding of the mechanisms driving diabetic heart disease, and to provide an accurate, reliable [...] Read more.
Diabetes is a global epidemic, with cardiovascular disease being the leading cause of death in diabetic patients. There is a pressing need for an in vitro model to aid understanding of the mechanisms driving diabetic heart disease, and to provide an accurate, reliable tool for drug testing. Human induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have potential as a disease modelling tool. There are several factors that drive molecular changes inside cardiomyocytes contributing to diabetic cardiomyopathy, including hyperglycaemia, lipotoxicity and hyperinsulinemia. Here we discuss these factors and how they can be seen in animal models and utilised in cell culture to mimic the diabetic heart. The use of human iPSC-CMs will allow for a greater understanding of disease pathogenesis and open up new avenues for drug testing. Full article
(This article belongs to the Special Issue The Studies of Metabolic Changes in Cardiac Stem Cells Differentiation)
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