scholarly journals Induced pluripotent stem-cell-derived cardiomyocytes: cardiac applications, opportunities, and challenges

2017 ◽  
Vol 95 (10) ◽  
pp. 1108-1116 ◽  
Author(s):  
Adrien Moreau ◽  
Mohamed Boutjdir ◽  
Mohamed Chahine
Keyword(s):  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Current State ◽  
Fundamental Research ◽  
Cardiac Disorders ◽  
Research Questions ◽  
Induced Pluripotent ◽  
New Treatments

Chronic diseases are the primary cause of mortality worldwide, accounting for 67% of deaths. One of the major challenges in developing new treatments is the lack of understanding of the exact underlying biological and molecular mechanisms. Chronic cardiovascular diseases are the single most common cause of death worldwide, and sudden deaths due to cardiac arrhythmias account for approximately 50% of all such cases. Traditional genetic screening for genes involved in cardiac disorders is labourious and frequently fails to detect the mutation that explains or causes the disorder. However, when mutations are identified, human induced pluripotent stem cells (hiPSCs) derived from affected patients make it possible to address fundamental research questions directly relevant to human health. As such, hiPSC technology has recently been used to model human diseases and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) thus offer a unique opportunity to investigate potential disease-causing genetic variants in their natural environment. The purpose of this review is to present the current state of knowledge regarding hiPSC-CMs, including their potential, limitations, and challenges and to discuss future prospects.

scholarly journals Disease Modeling of Mitochondrial Cardiomyopathy Using Patient-Specific Induced Pluripotent Stem Cells

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 981
Author(s):  
Takeshi Tokuyama ◽  
Razan Elfadil Ahmed ◽  
Nawin Chanthra ◽  
Tatsuya Anzai ◽  
Hideki Uosaki
Keyword(s):  
Pluripotent Stem Cells ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Drug Efficacy ◽  
Patient Specific ◽  
Experimental Platform ◽  
Mitochondrial Cardiomyopathy ◽  
Induced Pluripotent

Mitochondrial cardiomyopathy (MCM) is characterized as an oxidative phosphorylation disorder of the heart. More than 100 genetic variants in nuclear or mitochondrial DNA have been associated with MCM. However, the underlying molecular mechanisms linking genetic variants to MCM are not fully understood due to the lack of appropriate cellular and animal models. Patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) provide an attractive experimental platform for modeling cardiovascular diseases and predicting drug efficacy to such diseases. Here we introduce the pathological and therapeutic studies of MCM using iPSC-CMs and discuss the questions and latest strategies for research using iPSC-CMs.

scholarly journals Modeling Parkinson’s Disease Using Induced Pluripotent Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xinchao Hu ◽  
Chengyuan Mao ◽  
Liyuan Fan ◽  
Haiyang Luo ◽  
Zhengwei Hu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cellular Level ◽  
Patient Specific ◽  
Ubiquitin Protein Ligase ◽  
Induced Pluripotent

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The molecular mechanisms of PD at the cellular level involve oxidative stress, mitochondrial dysfunction, autophagy, axonal transport, and neuroinflammation. Induced pluripotent stem cells (iPSCs) with patient-specific genetic background are capable of directed differentiation into dopaminergic neurons. Cell models based on iPSCs are powerful tools for studying the molecular mechanisms of PD. The iPSCs used for PD studies were mainly from patients carrying mutations in synuclein alpha (SNCA), leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PARK2), cytoplasmic protein sorting 35 (VPS35), and variants in glucosidase beta acid (GBA). In this review, we summarized the advances in molecular mechanisms of Parkinson’s disease using iPSC models.

scholarly journals Technological Progress in Generation of Induced Pluripotent Stem Cells for Clinical Applications

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Seung-Ick Oh ◽  
Chang Kyu Lee ◽  
Kyung Jin Cho ◽  
Kyung-Ok Lee ◽  
Ssang-Goo Cho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chromosomal Abnormalities ◽  
Patient Specific ◽  
Current State ◽  
Reprogramming Efficiency ◽  
Induced Pluripotent ◽  
Viral Dna Integration ◽  
Medical Interest

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is achieved by viral-mediated transduction of defined transcription factors. Generation of iPSCs is of great medical interest as they have the potential to be a source of patient-specific cells. For the eventual goal of clinical application, it is necessary to overcome the limitations of low reprogramming efficiency and chromosomal abnormalities due to viral DNA integration. In this paper, we summarize the current state of reprogramming technology for generation of iPSCs and also discuss potential approaches to the development of safe iPSCs for personalized cell-based replacement therapy.

scholarly journals Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Daniel R. Bayzigitov ◽  
Sergey P. Medvedev ◽  
Elena V. Dementyeva ◽  
Sevda A. Bayramova ◽  
Evgeny A. Pokushalov ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Molecular Mechanisms ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Model Systems ◽  
Laboratory Animals ◽  
Patient Specific ◽  
Induced Pluripotent

Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

scholarly journals Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

2021 ◽  
Author(s):  
Foad J Rouhani ◽  
Xueqing Zou ◽  
Petr Danecek ◽  
Tauanne Dias Amarante ◽  
Gene Koh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent Stem Cell ◽  
Specific Model ◽  
Genomic Variation ◽  
Patient Specific ◽  
Sequencing Data ◽  
Induced Pluripotent

SummaryHuman Induced Pluripotent Stem Cells (hiPSC) are an established patient-specific model system where opportunities are emerging for cell-based therapies. We contrast hiPSCs derived from different tissues, skin and blood, in the same individual. We show extensive single-nucleotide mutagenesis in all hiPSC lines, although fibroblast-derived hiPSCs (F-hiPSCs) are particularly heavily mutagenized by ultraviolet(UV)-related damage. We utilize genome sequencing data on 454 F-hiPSCs and 44 blood-derived hiPSCs (B-hiPSCs) to gain further insights. Across 324 whole genome sequenced(WGS) F-hiPSCs derived by the Human Induced Pluripotent Stem Cell Initiative (HipSci), UV-related damage is present in ~72% of cell lines, sometimes causing substantial mutagenesis (range 0.25-15 per Mb). Furthermore, we find remarkable genomic heterogeneity between independent F-hiPSC clones derived from the same reprogramming process in the same donor, due to oligoclonal populations within fibroblasts. Combining WGS and exome-sequencing data of 452 HipSci F-hiPSCs, we identify 272 predicted pathogenic mutations in cancer-related genes, of which 21 genes were hit recurrently three or more times, involving 77 (17%) lines. Notably, 151 of 272 mutations were present in starting fibroblast populations suggesting that more than half of putative driver events in F-hiPSCs were acquired in vivo. In contrast, B-hiPSCs reprogrammed from erythroblasts show lower levels of genome-wide mutations (range 0.28-1.4 per Mb), no UV damage, but a strikingly high prevalence of acquired BCOR mutations of ~57%, indicative of strong selection pressure. All hiPSCs had otherwise stable, diploid genomes on karyotypic pre-screening, highlighting how copy-number-based approaches do not have the required resolution to detect widespread nucleotide mutagenesis. This work strongly suggests that models for cell-based therapies require detailed nucleotide-resolution characterization prior to clinical application.

scholarly journals Modelling Neurotropic Flavivirus Infection in Human Induced Pluripotent Stem Cell-Derived Systems

2019 ◽  
Vol 20 (21) ◽  
pp. 5404 ◽  
Author(s):  
Giovanna Desole ◽  
Alessandro Sinigaglia ◽  
Silvia Riccetti ◽  
Giulia Masi ◽  
Monia Pacenti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Viral Infections ◽  
Neurological Diseases ◽  
Induced Pluripotent Stem Cell ◽  
Immune Response Gene ◽  
Patient Specific ◽  
Lower Efficiency ◽  
Massive Cell Death ◽  
Induced Pluripotent

Generation of human induced pluripotent stem cells (hiPSCs) and their differentiation into a variety of cells and organoids have allowed setting up versatile, non-invasive, ethically sustainable, and patient-specific models for the investigation of the mechanisms of human diseases, including viral infections and host–pathogen interactions. In this study, we investigated and compared the infectivity and replication kinetics in hiPSCs, hiPSC-derived neural stem cells (NSCs) and undifferentiated neurons, and the effect of viral infection on host innate antiviral responses of representative flaviviruses associated with diverse neurological diseases, i.e., Zika virus (ZIKV), West Nile virus (WNV), and dengue virus (DENV). In addition, we exploited hiPSCs to model ZIKV infection in the embryo and during neurogenesis. The results of this study confirmed the tropism of ZIKV for NSCs, but showed that WNV replicated in these cells with much higher efficiency than ZIKV and DENV, inducing massive cell death. Although with lower efficiency, all flaviviruses could also infect pluripotent stem cells and neurons, inducing similar patterns of antiviral innate immune response gene expression. While showing the usefulness of hiPSC-based infection models, these findings suggest that additional virus-specific mechanisms, beyond neural tropism, are responsible for the peculiarities of disease phenotype in humans.

scholarly journals The Potential of Induced Pluripotent Stem Cells to Test Gene Therapy Approaches for Neuromuscular and Motor Neuron Disorders

2021 ◽  
Vol 9 ◽  
Author(s):  
Marisa Cappella ◽  
Sahar Elouej ◽  
Maria Grazia Biferi
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Motor Neuron ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Viral Vector ◽  
Patient Specific ◽  
Major Advance ◽  
Induced Pluripotent

The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) represents a major advance for the development of human disease models. The emerging of this technique fostered the concept of “disease in a dish,” which consists into the generation of patient-specific models in vitro. Currently, iPSCs are used to study pathological molecular mechanisms caused by genetic mutations and they are considered a reliable model for high-throughput drug screenings. Importantly, precision-medicine approaches to treat monogenic disorders exploit iPSCs potential for the selection and validation of lead candidates. For example, antisense oligonucleotides (ASOs) were tested with promising results in myoblasts or motor neurons differentiated from iPSCs of patients affected by either Duchenne muscular dystrophy or Amyotrophic lateral sclerosis. However, the use of iPSCs needs additional optimization to ensure translational success of the innovative strategies based on gene delivery through adeno associated viral vectors (AAV) for these diseases. Indeed, to establish an efficient transduction of iPSCs with AAV, several aspects should be optimized, including viral vector serotype, viral concentration and timing of transduction. This review will outline the use of iPSCs as a model for the development and testing of gene therapies for neuromuscular and motor neuron disorders. It will then discuss the advantages for the use of this versatile tool for gene therapy, along with the challenges associated with the viral vector transduction of iPSCs.

scholarly journals Insulin Resistance in Diabetes: The Promise of Using Induced Pluripotent Stem Cell Technology

2020 ◽  
Author(s):  
Ahmed Elsayed ◽  
Selvaraj Vimalraj ◽  
Manjula Nandakumar ◽  
Essam Abdelalim
Keyword(s):  
Insulin Resistance ◽  
Mouse Models ◽  
Pluripotent Stem Cells ◽  
Metabolic Disorders ◽  
Complex Disease ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Stem Cell Technology ◽  
Induced Pluripotent

In this review, we discuss the insulin resistance (IR) and its development in the insulin target tissues that leads to diabetes. Also, we highlight the use of induced pluripotent stem cells (iPSCs) to understand the mechanisms underlying the development of IR. IR is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Although there are currently several mouse models for both IR and T2D that had provided a lot of information about the disease, these models cannot recapitulate all the aspects of this complex disease as seen in each individual. Patient-specific iPSCs can overcome the hurdles faced with the classical mouse models for studying IR. iPSC technology can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of the genome editing and iPSCs may provide important information about the inherited factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.

Sign in / Sign up

Export Citation Format

Share Document