scholarly journals The fundamental discoveries in oxygen sensing: implications for heart diseases and cardiomyocytes maturation

Kosmos ◽  
2021 ◽  
Vol 69 (4) ◽  
pp. 563-577
Author(s):  
Monika Biniecka ◽  
Jan Wolnik ◽  
Józef Dulak
Keyword(s):  
Inflammatory Diseases ◽  
Heart Diseases ◽  
Oxygen Deficiency ◽  
Induced Pluripotent Stem Cell ◽  
Deep Impact ◽  
Chemical Stimuli ◽  
Induced Pluripotent ◽  
Physician Scientists ◽  
New Strategies

The 2019 Nobel Prize for Physiology or Medicine was awarded to three physician scientists, Drs. William G. Kaelin, Jr., Peter Ratcliffe and Gregg Semenza, for their research investigating how cells sense and adapt to oxygen levels.  Understanding the cellular adaptation to oxygen deficiency - hypoxia - has a deep impact on our knowledge of the pathogenesis of several conditions, including heart and inflammatory diseases, as well as tumours. HIF-1 is a transcription factor that plays an essential role in hypoxia-elicited gene responses. HIF-1 targets genes are involved in many pathways, such as cellular metabolism, survival and angiogenesis. Furthermore, hypoxia has been shown to impact the reprogramming process of somatic cells into induced pluripotent stem cell (iPSCs) and iPSC differentiation to cardiomyocytes (hiPSC-CMs). New strategies have been employed to improve the maturity of hiPSC-CMs, which includes the application of mechanistic or chemical stimuli and genetic/epigenetic manipulations. Currently, the role of hypoxia and energy metabolism in promoting maturation of hPSC-CMs is a subject of new studies.

Role of Mcl-1 in regulation of cell death in human induced pluripotent stem cell-derived cardiomyocytes in vitro

2018 ◽  
Vol 360 ◽  
pp. 88-98 ◽  
Author(s):  
Liang Guo ◽  
Sandy Eldridge ◽  
Michael Furniss ◽  
Jodie Mussio ◽  
Myrtle Davis
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent

scholarly journals Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell

2019 ◽  
Vol 115 (5) ◽  
pp. 949-959 ◽  
Author(s):  
Nazish Sayed ◽  
Mohamed Ameen ◽  
Joseph C Wu
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Association Studies ◽  
Induced Pluripotent Stem Cell ◽  
Human Diseases ◽  
Genome Wide Association Studies ◽  
Genomic Variants ◽  
Induced Pluripotent

Abstract Treatment of cancer has evolved in the last decade with the introduction of new therapies. Despite these successes, the lingering cardiotoxic side-effects from chemotherapy remain a major cause of morbidity and mortality in cancer survivors. These effects can develop acutely during treatment, or even years later. Although many risk factors can be identified prior to beginning therapy, unexpected toxicity still occurs, often with lasting consequences. Specifically, cardiotoxicity results in cardiac cell death, eventually leading to cardiomyopathy and heart failure. Certain risk factors may predispose an individual to experiencing adverse cardiovascular effects, and when unexpected cardiotoxicity occurs, it is generally managed with supportive care. Animal models of chemotherapy-induced cardiotoxicity have provided some mechanistic insights, but the precise mechanisms by which these drugs affect the heart remains unknown. Moreover, the genetic rationale as to why some patients are more susceptible to developing cardiotoxicity has yet to be determined. Many genome-wide association studies have identified genomic variants that could be associated with chemotherapy-induced cardiotoxicity, but the lack of validation has made these studies more speculative rather than definitive. With the advent of human induced pluripotent stem cell (iPSC) technology, researchers not only have the opportunity to model human diseases, but also to screen drugs for their efficacy and toxicity using human cell models. Furthermore, it allows us to conduct validation studies to confirm the role of genomic variants in human diseases. In this review, we discuss the role of iPSCs in modelling chemotherapy-induced cardiotoxicity.

scholarly journals Human Induced Pluripotent Stem Cell-Derived Vascular Cells: Recent Progress and Future Directions

2021 ◽  
Vol 8 (11) ◽  
pp. 148
Author(s):  
Jee Eun Oh ◽  
Cholomi Jung ◽  
Young-sup Yoon
Keyword(s):  
Animal Models ◽  
Induced Pluripotent Stem Cell ◽  
Great Promise ◽  
Vascular Cells ◽  
Future Directions ◽  
Tissue Repair And Regeneration ◽  
Therapeutic Benefits ◽  
Cardiovascular Regeneration ◽  
Induced Pluripotent

Human induced pluripotent stem cells (hiPSCs) hold great promise for cardiovascular regeneration following ischemic injury. Considerable effort has been made toward the development and optimization of methods to differentiate hiPSCs into vascular cells, such as endothelial and smooth muscle cells (ECs and SMCs). In particular, hiPSC-derived ECs have shown robust potential for promoting neovascularization in animal models of cardiovascular diseases, potentially achieving significant and sustained therapeutic benefits. However, the use of hiPSC-derived SMCs that possess high therapeutic relevance is a relatively new area of investigation, still in the earlier investigational stages. In this review, we first discuss different methodologies to derive vascular cells from hiPSCs with a particular emphasis on the role of key developmental signals. Furthermore, we propose a standardized framework for assessing and defining the EC and SMC identity that might be suitable for inducing tissue repair and regeneration. We then highlight the regenerative effects of hiPSC-derived vascular cells on animal models of myocardial infarction and hindlimb ischemia. Finally, we address several obstacles that need to be overcome to fully implement the use of hiPSC-derived vascular cells for clinical application.

scholarly journals 3213 Unraveling the role of Phospholamban (PLN) in humans via the characterization of Induced Pluripotent Stem Cell (iPSC) Cardiomyocytes (CM) derived from carriers of a lethal PLN mutation

2019 ◽  
Vol 3 (s1) ◽  
pp. 26-26
Author(s):  
Maria Giovanna Trivieri ◽  
Francesca Stillitano ◽  
Delaine Ceholski ◽  
Irene Turnbull ◽  
Kevin Costa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
State Of The Art ◽  
Induced Pluripotent Stem Cell ◽  
Relevant Model ◽  
Study Population ◽  
Induced Pluripotent ◽  
Ca Homeostasis

OBJECTIVES/SPECIFIC AIMS: To study the biology of Phosholamban (PLN) in a human relevant model. METHODS/STUDY POPULATION: State of the art stem-cell technologies using iPSC-CMs derived from carriers of a lethal PLN mutation. RESULTS/ANTICIPATED RESULTS: Our preliminary data demonstrate that this particular PLN mutation (L39) results in reduced expression and mis-localization of PLN as well as increased incidence of early after depolarization in isolated iPSC-CMs. DISCUSSION/SIGNIFICANCE OF IMPACT: Phospholamban (PLN) is a critical regulator of Ca++ homeostasis yet many uncertainties still remain regarding its role in humans. Our study will provide unique insights into the pathophysiology of this protein in HF.

scholarly journals Excess Lipin enzyme activity contributes to TOR1A recessive disease and DYT-TOR1A dystonia

Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1746-1765 ◽  
Author(s):  
Ana Cascalho ◽  
Joyce Foroozandeh ◽  
Lise Hennebel ◽  
Jef Swerts ◽  
Christine Klein ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Phosphatidic Acid ◽  
Mouse Models ◽  
Disease Model ◽  
Induced Pluripotent Stem Cell ◽  
Motor Dysfunction ◽  
Neurological Dysfunction ◽  
Knock Out ◽  
Induced Pluripotent

Abstract TOR1A/TorsinA mutations cause two incurable diseases: a recessive congenital syndrome that can be lethal, and a dominantly-inherited childhood-onset dystonia (DYT-TOR1A). TorsinA has been linked to phosphatidic acid lipid metabolism in Drosophila melanogaster. Here we evaluate the role of phosphatidic acid phosphatase (PAP) enzymes in TOR1A diseases using induced pluripotent stem cell-derived neurons from patients, and mouse models of recessive Tor1a disease. We find that Lipin PAP enzyme activity is abnormally elevated in human DYT-TOR1A dystonia patient cells and in the brains of four different Tor1a mouse models. Its severity also correlated with the dosage of Tor1a/TOR1A mutation. We assessed the role of excess Lipin activity in the neurological dysfunction of Tor1a disease mouse models by interbreeding these with Lpin1 knock-out mice. Genetic reduction of Lpin1 improved the survival of recessive Tor1a disease-model mice, alongside suppressing neurodegeneration, motor dysfunction, and nuclear membrane pathology. These data establish that TOR1A disease mutations cause abnormal phosphatidic acid metabolism, and suggest that approaches that suppress Lipin PAP enzyme activity could be therapeutically useful for TOR1A diseases.

A PRC2-Dependent Repressive Role of PRDM14 in Human Embryonic Stem Cells and Induced Pluripotent Stem Cell Reprogramming

Stem Cells ◽  
2013 ◽  
Vol 31 (4) ◽  
pp. 682-692 ◽  
Author(s):  
Yun-Shen Chan ◽  
Jonathan Göke ◽  
Xinyi Lu ◽  
Nandini Venkatesan ◽  
Bo Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Pluripotent Stem Cell ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Cell Reprogramming ◽  
Induced Pluripotent

scholarly journals Examining the Protective Role of ErbB2 Modulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

2014 ◽  
Vol 141 (2) ◽  
pp. 547-559 ◽  
Author(s):  
Sandy Eldridge ◽  
Liang Guo ◽  
Jodie Mussio ◽  
Mike Furniss ◽  
John Hamre ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Protective Role ◽  
Induced Pluripotent
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