Engineering Cardiac Tissues from Pluripotent Stem Cells for Drug Screening and Studies of Cell Maturation

A mere 9 years have passed since the revolutionary report describing the derivation of induced pluripotent stem cells from human fibroblasts and the first in-patient translational use of cells obtained from these stem cells has already been achieved. From the perspectives of clinicians and researchers alike, the promise of induced pluripotent stem cells is alluring if somewhat beguiling. It is now evident that this technology is nascent and many areas for refinement have been identified and need to be considered before induced pluripotent stem cells can be routinely used to stratify, treat and cure patients, and to faithfully model diseases for drug screening purposes. This review specifically addresses the pioneering approaches to improve induced pluripotent stem cell based models of nonischaemic cardiomyopathy.

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Tubular Cardiac Tissues Derived from Human Induced Pluripotent Stem Cells Generate Pulse Pressure In Vivo

Scientific Reports ◽

10.1038/srep45499 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 27

Author(s):

Hiroyoshi Seta ◽

Katsuhisa Matsuura ◽

Hidekazu Sekine ◽

Kenji Yamazaki ◽

Tatsuya Shimizu

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pulse Pressure ◽

Pluripotent Stem Cells ◽

Cardiac Tissues ◽

Induced Pluripotent

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Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells

Acta Pharmacologica Sinica ◽

10.1038/aps.2013.63 ◽

2013 ◽

Vol 34 (6) ◽

pp. 755-764 ◽

Cited By ~ 38

Author(s):

Xiao-hong Xu ◽

Zhong Zhong

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Neurological Diseases ◽

Induced Pluripotent

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Human Embryos, Induced Pluripotent Stem Cells, and Organoids: Models to Assess the Effects of Environmental Plastic Pollution

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.709183 ◽

2021 ◽

Vol 9 ◽

Author(s):

Dragana Miloradovic ◽

Dragica Pavlovic ◽

Marina Gazdic Jankovic ◽

Sandra Nikolic ◽

Milos Papic ◽

...

Keyword(s):

Stem Cells ◽

Animal Models ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

New Technologies ◽

Human Embryos ◽

Plastic Pollution ◽

Potential Health ◽

Induced Pluripotent

For a long time, animal models were used to mimic human biology and diseases. However, animal models are not an ideal solution due to numerous interspecies differences between humans and animals. New technologies, such as human-induced pluripotent stem cells and three-dimensional (3D) cultures such as organoids, represent promising solutions for replacing, refining, and reducing animal models. The capacity of organoids to differentiate, self-organize, and form specific, complex, biologically suitable structures makes them excellent in vitro models of development and disease pathogenesis, as well as drug-screening platforms. Despite significant potential health advantages, further studies and considerable nuances are necessary before their clinical use. This article summarizes the definition of embryoids, gastruloids, and organoids and clarifies their appliance as models for early development, diseases, environmental pollution, drug screening, and bioinformatics.

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Nanomedicine-based Curcumin Approach Improved ROS Damage in Best Dystrophy-specific Induced Pluripotent Stem Cells

Cell Transplantation ◽

10.1177/0963689719860130 ◽

2019 ◽

Vol 28 (11) ◽

pp. 1345-1357 ◽

Cited By ~ 2

Author(s):

Tai-Chi Lin ◽

Yi-Ying Lin ◽

Chih-Chen Hsu ◽

Yi-Ping Yang ◽

Chang-Hao Yang ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Retinal Pigment ◽

Retinal Pigment Epithelial Cells ◽

Patient Specific ◽

Macular Dystrophy ◽

Junction Protein ◽

Induced Pluripotent

Best dystrophy (BD), also termed best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and can cause central visual loss. Unfortunately, there is no clear definite therapy for BD or improving the visual function on this progressive disease. The human induced pluripotent stem cell (iPSC) system has been recently applied as an effective tool for genetic consultation and chemical drug screening. In this study, we developed patient-specific induced pluripotent stem cells (BD-iPSCs) from BD patient-derived dental pulp stromal cells and then differentiated BD-iPSCs into retinal pigment epithelial cells (BD-RPEs). BD-RPEs were used as an expandable platform for in vitro candidate drug screening. Compared with unaffected sibling-derived iPSC-derived RPE cells (Ctrl-RPEs), BD-RPEs exhibited typical RPE-specific markers with a lower expression of the tight junction protein ZO-1 and Bestrophin-1 (BEST1), as well as reduced phagocytic capabilities. Notably, among all candidate drugs, curcumin was the most effective for upregulating both the BEST1 and ZO-1 genes in BD-RPEs. Using the iPSC-based drug-screening platform, we further found that curcumin can significantly improve the mRNA expression levels of Best gene in BD-iPSC-derived RPEs. Importantly, we demonstrated that curcumin-loaded PLGA nanoparticles (Cur-NPs) were efficiently internalized by BD-RPEs. The Cur-NPs-based controlled release formulation further increased the expression of ZO-1 and Bestrophin-1, and promoted the function of phagocytosis and voltage-dependent calcium channels in BD-iPSC-derived RPEs. We further demonstrated that Cur-NPs enhanced the expression of antioxidant enzymes with a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Collectively, these data supported that Cur-NPs provide a potential cytoprotective effect by regulating the anti-oxidative abilities of degenerated RPEs. In addition, the application of patient-specific iPSCs provides an effective platform for drug screening and personalized medicine in incurable diseases.

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Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation

Cell Death and Disease ◽

10.1038/cddis.2015.374 ◽

2016 ◽

Vol 7 (2) ◽

pp. e2105-e2105 ◽

Cited By ~ 25

Author(s):

S Blondel ◽

A-L Egesipe ◽

P Picardi ◽

A-L Jaskowiak ◽

M Notarnicola ◽

...

Keyword(s):

Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells

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Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening

Translational Psychiatry ◽

10.1038/tp.2013.71 ◽

2013 ◽

Vol 3 (8) ◽

pp. e294-e294 ◽

Cited By ~ 59

Author(s):

C Boissart ◽

A Poulet ◽

P Georges ◽

H Darville ◽

E Julita ◽

...

Keyword(s):

Stem Cells ◽

High Throughput ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Cortical Neurons ◽

Disease Modeling ◽

Human Pluripotent Stem Cells ◽

Psychiatric Disease ◽

High Throughput Drug Screening

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Engineered heart tissues and induced pluripotent stem cells: Macro- and microstructures for disease modeling, drug screening, and translational studies

Advanced Drug Delivery Reviews ◽

10.1016/j.addr.2015.09.010 ◽

2016 ◽

Vol 96 ◽

pp. 234-244 ◽

Cited By ~ 83

Author(s):

Evangeline Tzatzalos ◽

Oscar J. Abilez ◽

Praveen Shukla ◽

Joseph C. Wu

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Translational Studies ◽

Induced Pluripotent ◽

Engineered Heart Tissues

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Bioengineering Clinically Relevant Cardiomyocytes and Cardiac Tissues from Pluripotent Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22063005 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3005

Author(s):

Emma Claire James ◽

Eva Tomaskovic-Crook ◽

Jeremy Micah Crook

Keyword(s):

Stem Cells ◽

Heart Disease ◽

Electric Fields ◽

Pluripotent Stem Cells ◽

Heart Development ◽

Disease Patient ◽

Toxicity Testing ◽

Model Systems ◽

Patient Specific ◽

Cardiac Tissues

The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. New insights gleaned from embryonic heart development have progressed the precise production of subtype-specific hiPSC-derived cardiomyocytes; however, their physiological immaturity severely limits their utility as model systems and their use for drug screening and cell therapy. The long-entrenched challenges in this field are being addressed by innovative bioengingeering technologies that incorporate biophysical, biochemical and more recently biomimetic electrical cues, with the latter having the potential to be used to both direct hiPSC differentiation and augment maturation and the function of derived cardiomyocytes and cardiac tissues by mimicking endogenous electric fields.

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