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Cells
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Applications of Stem Cells in Cardiovascular Functional Genomics
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Applications of Stem Cells in Cardiovascular Functional Genomics

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 15120

Special Issue Editor

Prof. Dr. Agapios Sachinidis

E-Mail Website
Guest Editor
Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 39, 50931 Cologne, Germany
Interests: molecular genetics and genomics of stem cells; stem cell cardiovascular genomics; developmental/differentiation; toxicity gene signatures and pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The regular development and maintenance of an intact cardiovascular system involves fine-tuned complex gene expression pathways which coordinate the development and function of the cardiovascular system. The field of cardiovascular functional genomics aims to identify the regular genes and signal transduction pathways in order to obtain a better understanding of the development and progress of cardiovascular diseases (CVDs). Because of the strict ethical aspects, to date functional genomics studies of the cardiovascular system have been executed using small animal studies. However, not all animal functional genomics studies can be transferred to humans. Moreover, even though animal studies have significantly contributed to the functional genomics of the cardiovascular system (CVS), these studies are very costly and time-consuming and cannot be executed in a high-throughput approach. Embryonic stem cells (ESCs) and recently induced pluripotent stem cells (iPSCs) have been shown to partly recapitulate embryonic development in vivo. Moreover, somatic cell derivatives from pluripotent stem cells (PSCs) (ESCs and iPSCs) in combination with advanced genomics technologies are applied to the discovery of disease-associated and cardiovascular toxicity gene networks involved in the development of CVDs. It is hoped that progress in this field will contribute to personalized medicine for developing better and novel therapeutic tools for the treatment of CVDs. The present topic is focused on the latest progress in functional genomics (including epigenomics) of the cardiovascular system based on the PSC model. Emphasis will also be placed on the question of how this emerging field will contribute to the discovery of novel mechanisms and pathways which are relevant to therapeutic applications of CVDs. In addition to original manuscripts, review manuscripts discussing limitations and advances of this field will be also considered for publication.

Prof. Agapios Sachinidis
Guest Editor

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Keywords

  • Pluripotent stem cells
  • Functional genomic and epigenomics
  • Signal transduction pathways
  • Cardiovascular diseases
  • Cardiovascular toxicity

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Published Papers (4 papers)

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Research

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18 pages, 3747 KiB  
Article
Detection of Novel Potential Regulators of Stem Cell Differentiation and Cardiogenesis through Combined Genome-Wide Profiling of Protein-Coding Transcripts and microRNAs
by Rui Machado, Agapios Sachinidis and Matthias E. Futschik
Cells 2021, 10(9), 2477; https://doi.org/10.3390/cells10092477 - 18 Sep 2021
Cited by 1 | Viewed by 2971
Abstract
In vitro differentiation of embryonic stem cells (ESCs) provides a convenient basis for the study of microRNA-based gene regulation that is relevant for early cardiogenic processes. However, to which degree insights gained from in vitro differentiation models can be readily transferred to the [...] Read more.
In vitro differentiation of embryonic stem cells (ESCs) provides a convenient basis for the study of microRNA-based gene regulation that is relevant for early cardiogenic processes. However, to which degree insights gained from in vitro differentiation models can be readily transferred to the in vivo system remains unclear. In this study, we profiled simultaneous genome-wide measurements of mRNAs and microRNAs (miRNAs) of differentiating murine ESCs (mESCs) and integrated putative miRNA-gene interactions to assess miRNA-driven gene regulation. To identify interactions conserved between in vivo and in vitro, we combined our analysis with a recent transcriptomic study of early murine heart development in vivo. We detected over 200 putative miRNA–mRNA interactions with conserved expression patterns that were indicative of gene regulation across the in vitro and in vivo studies. A substantial proportion of candidate interactions have been already linked to cardiogenesis, supporting the validity of our approach. Notably, we also detected miRNAs with expression patterns that closely resembled those of key developmental transcription factors. The approach taken in this study enabled the identification of miRNA interactions in in vitro models with potential relevance for early cardiogenic development. Such comparative approaches will be important for the faithful application of stem cells in cardiovascular research. Full article
(This article belongs to the Special Issue Applications of Stem Cells in Cardiovascular Functional Genomics)
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19 pages, 4905 KiB  
Article
Generation, Characterization, and Application of Inducible Proliferative Adult Human Epicardium-Derived Cells
by Yang Ge, Anke M. Smits, Jia Liu, Juan Zhang, Thomas J. van Brakel, Marie José T. H. Goumans, Monique R. M. Jongbloed and Antoine A. F. de Vries
Cells 2021, 10(8), 2064; https://doi.org/10.3390/cells10082064 - 12 Aug 2021
Cited by 4 | Viewed by 2822
Abstract
Rationale: In recent decades, the great potential of human epicardium-derived cells (EPDCs) as an endogenous cell source for cardiac regeneration has been recognized. The limited availability and low proliferation capacity of primary human EPDCs and phenotypic differences between EPDCs obtained from different individuals [...] Read more.
Rationale: In recent decades, the great potential of human epicardium-derived cells (EPDCs) as an endogenous cell source for cardiac regeneration has been recognized. The limited availability and low proliferation capacity of primary human EPDCs and phenotypic differences between EPDCs obtained from different individuals hampers their reproducible use for experimental studies. Aim: To generate and characterize inducible proliferative adult human EPDCs for use in fundamental and applied research. Methods and results: Inducible proliferation of human EPDCs was achieved by doxycycline-controlled expression of simian virus 40 large T antigen (LT) with a repressor-based lentiviral Tet-On system. In the presence of doxycycline, these inducible EPDCs (iEPDCs) displayed high and long-term proliferation capacity. After doxycycline removal, LT expression ceased and the iEPDCs regained their cuboidal epithelial morphology. Similar to primary EPDCs, iEPDCs underwent an epithelial-to-mesenchymal transition (EMT) after stimulation with transforming growth factor β3. This was confirmed by reverse transcription-quantitative polymerase chain reaction analysis of epithelial and mesenchymal marker gene expression and (immuno) cytochemical staining. Collagen gel-based cell invasion assays demonstrated that mesenchymal iEPDCs, like primary EPDCs, possess increased invasion and migration capacities as compared to their epithelial counterparts. Mesenchymal iEPDCs co-cultured with sympathetic ganglia stimulated neurite outgrowth similarly to primary EPDCs. Conclusion: Using an inducible LT expression system, inducible proliferative adult human EPDCs were generated displaying high proliferative capacity in the presence of doxycycline. These iEPDCs maintain essential epicardial characteristics with respect to morphology, EMT ability, and paracrine signaling following doxycycline removal. This renders iEPDCs a highly useful new in vitro model for studying human epicardial properties. Full article
(This article belongs to the Special Issue Applications of Stem Cells in Cardiovascular Functional Genomics)
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Review

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20 pages, 1101 KiB  
Review
Regenerating Damaged Myocardium: A Review of Stem-Cell Therapies for Heart Failure
by Dihan Fan, Hanrong Wu, Kaichao Pan, Huashan Peng and Rongxue Wu
Cells 2021, 10(11), 3125; https://doi.org/10.3390/cells10113125 - 11 Nov 2021
Cited by 5 | Viewed by 4875
Abstract
Cardiovascular disease (CVD) is one of the contributing factors to more than one-third of human mortality and the leading cause of death worldwide. The death of cardiac myocyte is a fundamental pathological process in cardiac pathologies caused by various heart diseases, including myocardial [...] Read more.
Cardiovascular disease (CVD) is one of the contributing factors to more than one-third of human mortality and the leading cause of death worldwide. The death of cardiac myocyte is a fundamental pathological process in cardiac pathologies caused by various heart diseases, including myocardial infarction. Thus, strategies for replacing fibrotic tissue in the infarcted region with functional myocardium have long been a goal of cardiovascular research. This review begins by briefly discussing a variety of somatic stem- and progenitor-cell populations that were frequently studied in early investigations of regenerative myocardial therapy and then focuses primarily on pluripotent stem cells (PSCs), especially induced-pluripotent stem cells (iPSCs), which have emerged as perhaps the most promising source of cardiomyocytes for both therapeutic applications and drug testing. We also describe attempts to generate cardiomyocytes directly from cardiac fibroblasts (i.e., transdifferentiation), which, if successful, may enable the pool of endogenous cardiac fibroblasts to be used as an in-situ source of cardiomyocytes for myocardial repair. Full article
(This article belongs to the Special Issue Applications of Stem Cells in Cardiovascular Functional Genomics)
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Graphical abstract

17 pages, 349 KiB  
Review
Application of the Pluripotent Stem Cells and Genomics in Cardiovascular Research—What We Have Learnt and Not Learnt until Now
by Michael Simeon, Seema Dangwal, Agapios Sachinidis and Michael Xavier Doss
Cells 2021, 10(11), 3112; https://doi.org/10.3390/cells10113112 - 10 Nov 2021
Cited by 4 | Viewed by 3303
Abstract
Personalized regenerative medicine and biomedical research have been galvanized and revolutionized by human pluripotent stem cells in combination with recent advances in genomics, artificial intelligence, and genome engineering. More recently, we have witnessed the unprecedented breakthrough life-saving translation of mRNA-based vaccines for COVID-19 [...] Read more.
Personalized regenerative medicine and biomedical research have been galvanized and revolutionized by human pluripotent stem cells in combination with recent advances in genomics, artificial intelligence, and genome engineering. More recently, we have witnessed the unprecedented breakthrough life-saving translation of mRNA-based vaccines for COVID-19 to contain the global pandemic and the investment in billions of US dollars in space exploration projects and the blooming space-tourism industry fueled by the latest reusable space vessels. Now, it is time to examine where the translation of pluripotent stem cell research stands currently, which has been touted for more than the last two decades to cure and treat millions of patients with severe debilitating degenerative diseases and tissue injuries. This review attempts to highlight the accomplishments of pluripotent stem cell research together with cutting-edge genomics and genome editing tools and, also, the promises that have still not been transformed into clinical applications, with cardiovascular research as a case example. This review also brings to our attention the scientific and socioeconomic challenges that need to be effectively addressed to see the full potential of pluripotent stem cells at the clinical bedside. Full article
(This article belongs to the Special Issue Applications of Stem Cells in Cardiovascular Functional Genomics)
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