Concise Review: Induced Pluripotent Stem Cells as New Model Systems in Oncology

Congenital heart disease (CHD) is the most common cause of infant death associated with birth defects. Recent next-generation genome sequencing has uncovered novel genetic etiologies of CHD, from inherited and de novo variants to non-coding genetic variants. The next phase of understanding the genetic contributors of CHD will be the functional illustration and validation of this genome sequencing data in cellular and animal model systems. Human induced pluripotent stem cells (iPSCs) have opened up new horizons to investigate genetic mechanisms of CHD using clinically relevant and patient-specific cardiac cells such as cardiomyocytes, endothelial/endocardial cells, cardiac fibroblasts and vascular smooth muscle cells. Using cutting-edge CRISPR/Cas9 genome editing tools, a given genetic variant can be corrected in diseased iPSCs and introduced to healthy iPSCs to define the pathogenicity of the variant and molecular basis of CHD. In this review, we discuss the recent progress in genetics of CHD deciphered by large-scale genome sequencing and explore how genome-edited patient iPSCs are poised to decode the genetic etiologies of CHD by coupling with single-cell genomics and organoid technologies.

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Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells

Stem Cells ◽

10.1002/stem.2070 ◽

2015 ◽

Vol 33 (9) ◽

pp. 2643-2651 ◽

Cited By ~ 27

Author(s):

Chunbo Yang ◽

Jumana Al-Aama ◽

Miodrag Stojkovic ◽

Bernard Keavney ◽

Andrew Trafford ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Cardiac Disease ◽

Disease Modeling ◽

Concise Review ◽

Induced Pluripotent

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Concise Review: New Paradigms for Down Syndrome Research Using Induced Pluripotent Stem Cells: Tackling Complex Human Genetic Disease

Stem Cells Translational Medicine ◽

10.5966/sctm.2012-0117 ◽

2013 ◽

Vol 2 (3) ◽

pp. 175-184 ◽

Cited By ~ 10

Author(s):

James A. Briggs ◽

Elizabeth A. Mason ◽

Dmitry A. Ovchinnikov ◽

Christine A. Wells ◽

Ernst J. Wolvetang

Keyword(s):

Stem Cells ◽

Down Syndrome ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Genetic Disease ◽

Human Genetic Disease ◽

Concise Review ◽

Induced Pluripotent

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A New Model for Studying Interaction between Hepatitis B Virus and Host Cells Derived from Human Induced Pluripotent Stem Cells

Journal of Hepatology ◽

10.1016/s0168-8278(16)00621-8 ◽

2016 ◽

Vol 64 (2) ◽

pp. S396-S397

Author(s):

S. Kaneko ◽

S. Kakinuma ◽

Y. Asahina ◽

A. Kamiya ◽

S. Nitta ◽

...

Keyword(s):

Stem Cells ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Host Cells ◽

New Model ◽

B Virus ◽

Induced Pluripotent

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Induced pluripotent stem cells in psychiatry: a critical review

10.31219/osf.io/aw2hk ◽

2021 ◽

Author(s):

Alejandro De Los Angeles ◽

Kristen Brennand ◽

Nicola Hall ◽

Michael Fernando ◽

Paul Harrison ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Statistical Power ◽

Model Systems ◽

Neural Cells ◽

Case Control Studies ◽

Pathophysiological Mechanisms ◽

Induced Pluripotent ◽

Cellular Phenotypes

A key challenge in psychiatry research is the development of high-fidelity model systems that can be experimentally manipulated to explore and test pathophysiological mechanisms of illness. In this respect, the emerging capacity to derive neural cells and circuits from human induced pluripotent stem cells (iPSCs) has generated significant excitement. This review aims to provide a critical appraisal of the potential for iPSCs in illuminating pathophysiological mechanisms and to situate them in the wider technical landscape. We discuss the selection of iPSC phenotypes relevant to psychiatry, the information that researchers can draw on to help guide these decisions, and how researchers choose between the use of 2D cultures, vs. more complex 3D model systems. We discuss the strengths and limitations of current models, and the challenges and opportunities that they present. Finally, we discuss the potential of iPSC-based model systems for clarifying the mechanisms underlying genetic risk for psychiatry, and the steps that will be needed to ensure that robust and reliable conclusions can be drawn. We argue that, whilst iPSC-based models are ideally placed to study fundamental processes occurring within and between neural cells, they are often less well-suited for case-control studies, given issues relating to statistical power and the challenges in identifying which cellular phenotypes are meaningful at the level of the whole individual. Our aim is to highlight the importance of considering the hypotheses of a given study to guide decisions about which, if any, iPSC-based system is most appropriate to address it.

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The utilisation of organoids and macrophages derived from Human induced pluripotent stem cells as model systems to investigate host-bacterial interactions

Access Microbiology ◽

10.1099/acmi.ac2019.po0548 ◽

2019 ◽

Vol 1 (1A) ◽

Author(s):

Christine Hale ◽

Leanne Kane ◽

Matthew Dorman ◽

Nicholas Thomson

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Induced Pluripotent Stem Cell ◽

Cell Types ◽

Genetically Engineered ◽

Model Systems ◽

Host Cells ◽

Bacterial Interactions ◽

Induced Pluripotent

Using human induced pluripotent stem cell (hiPSC) technology we are developing methods to examine host-bacterial interactions. Due to the fact that undifferentiated human induced pluripotent stem cells are amenable to genetic engineering, can be cultured indefinitely and can further be differentiated into multiple cell types, we are exploiting both organoid and macrophage systems to investigate the interactions between host cells and diarrhoeal pathogens, including enterotoxigenic Escherichia coli and Vibrio cholerae. Utilising both wild type and relevant knockout hiPSC lines we are probing both initial interactions and subsequent utilisation of pathways for the effects of toxins. The further analysis of genetically engineered bacteria extend the usefulness of this model system, and complement the availability of mutant host cells, towards the simultaneous genetic analysis of both pathogen and host.

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Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural Stem Cells and Dopaminergic Lineage

International Journal of Molecular Sciences ◽

10.3390/ijms19092788 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2788 ◽

Cited By ~ 5

Author(s):

Guang Yang ◽

Hyenjong Hong ◽

April Torres ◽

Kristen Malloy ◽

Gourav Choudhury ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Cell Lines ◽

Pluripotent Stem Cells ◽

In Vitro Models ◽

The Body ◽

Model Systems ◽

Induced Pluripotent

Humans and nonhuman primates (NHP) are similar in behavior and in physiology, specifically the structure, function, and complexity of the immune system. Thus, NHP models are desirable for pathophysiology and pharmacology/toxicology studies. Furthermore, NHP-derived induced pluripotent stem cells (iPSCs) may enable transformative developmental, translational, or evolutionary studies in a field of inquiry currently hampered by the limited availability of research specimens. NHP-iPSCs may address specific questions that can be studied back and forth between in vitro cellular assays and in vivo experimentations, an investigational process that in most cases cannot be performed on humans because of safety and ethical issues. The use of NHP model systems and cell specific in vitro models is evolving with iPSC-based three-dimensional (3D) cell culture systems and organoids, which may offer reliable in vitro models and reduce the number of animals used in experimental research. IPSCs have the potential to give rise to defined cell types of any organ of the body. However, standards for deriving defined and validated NHP iPSCs are missing. Standards for deriving high-quality iPSC cell lines promote rigorous and replicable scientific research and likewise, validated cell lines reduce variability and discrepancies in results between laboratories. We have derived and validated NHP iPSC lines by confirming their pluripotency and propensity to differentiate into all three germ layers (ectoderm, mesoderm, and endoderm) according to standards and measurable limits for a set of marker genes. The iPSC lines were characterized for their potential to generate neural stem cells and to differentiate into dopaminergic neurons. These iPSC lines are available to the scientific community. NHP-iPSCs fulfill a unique niche in comparative genomics to understand gene regulatory principles underlying emergence of human traits, in infectious disease pathogenesis, in vaccine development, and in immunological barriers in regenerative medicine.

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