A microfluidic gradient device for drug screening with human iPSC-derived motoneurons

The Analyst ◽  
2020 ◽  
Vol 145 (8) ◽  
pp. 3081-3089 ◽  
Author(s):  
Sung Joon Mo ◽  
Ju-Hyun Lee ◽  
Hyeon Gi Kye ◽  
Jong Min Lee ◽  
Eun-Joong Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Drug Screening ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Screening System ◽  
Induced Pluripotent ◽  
Gradient Device ◽  
Human Ipsc

We developed a microfluidic gradient device to utilize as a drug screening system with human induced pluripotent stem cell (hiPSC)-derived motoneurons.

scholarly journals Young at Heart: Pioneering Approaches to Model Nonischaemic Cardiomyopathy with Induced Pluripotent Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Aoife Gowran ◽  
Marco Rasponi ◽  
Roberta Visone ◽  
Patrizia Nigro ◽  
Gianluca L. Perrucci ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Drug Screening ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Human Fibroblasts ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent

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.

scholarly journals Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies

2019 ◽  
Vol 20 (18) ◽  
pp. 4381 ◽  
Author(s):  
Andreas Brodehl ◽  
Hans Ebbinghaus ◽  
Marcus-André Deutsch ◽  
Jan Gummert ◽  
Anna Gärtner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Promising Alternative ◽  
Human Ipscs ◽  
Genetic Landscape ◽  
Inherited Cardiomyopathies ◽  
Induced Pluripotent ◽  
Human Ipsc

In the last few decades, many pathogenic or likely pathogenic genetic mutations in over hundred different genes have been described for non-ischemic, genetic cardiomyopathies. However, the functional knowledge about most of these mutations is still limited because the generation of adequate animal models is time-consuming and challenging. Therefore, human induced pluripotent stem cells (iPSCs) carrying specific cardiomyopathy-associated mutations are a promising alternative. Since the original discovery that pluripotency can be artificially induced by the expression of different transcription factors, various patient-specific-induced pluripotent stem cell lines have been generated to model non-ischemic, genetic cardiomyopathies in vitro. In this review, we describe the genetic landscape of non-ischemic, genetic cardiomyopathies and give an overview about different human iPSC lines, which have been developed for the disease modeling of inherited cardiomyopathies. We summarize different methods and protocols for the general differentiation of human iPSCs into cardiomyocytes. In addition, we describe methods and technologies to investigate functionally human iPSC-derived cardiomyocytes. Furthermore, we summarize novel genome editing approaches for the genetic manipulation of human iPSCs. This review provides an overview about the genetic landscape of inherited cardiomyopathies with a focus on iPSC technology, which might be of interest for clinicians and basic scientists interested in genetic cardiomyopathies.

scholarly journals Drug Screening Using a Library of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes Reveals Disease-Specific Patterns of Cardiotoxicity

Circulation ◽  
2013 ◽  
Vol 127 (16) ◽  
pp. 1677-1691 ◽  
Author(s):  
Ping Liang ◽  
Feng Lan ◽  
Andrew S. Lee ◽  
Tingyu Gong ◽  
Veronica Sanchez-Freire ◽  
...  
Keyword(s):  
Stem Cell ◽  
Drug Screening ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent ◽  
Disease Specific

scholarly journals Modeling Neurological Disorders with Human Pluripotent Stem Cell-Derived Astrocytes

2019 ◽  
Vol 20 (16) ◽  
pp. 3862 ◽  
Author(s):  
Mika Suga ◽  
Takayuki Kondo ◽  
Haruhisa Inoue
Keyword(s):  
Stem Cell ◽  
Neurological Disorders ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Human Diseases ◽  
Human Pluripotent Stem Cell ◽  
Human Astrocytes ◽  
Induced Pluripotent ◽  
Human Ipsc

Astrocytes play vital roles in neurological disorders. The use of human induced pluripotent stem cell (iPSC)-derived astrocytes provides a chance to explore the contributions of astrocytes in human diseases. Here we review human iPSC-based models for neurological disorders associated with human astrocytes and discuss the points of each model.

Identification of Drug Transporter Genomic Variants and Inhibitors that Protect Against Doxorubicin-Induced Cardiotoxicity

Circulation ◽  
2021 ◽  
Author(s):  
Tarek Magdy ◽  
Mariam Jouni ◽  
Hui-Hsuan Kuo ◽  
Carly J. Weddle ◽  
Davi Lyra-Leite ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fine Mapping ◽  
Drug Screening ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Causal Variant ◽  
Patient Specific ◽  
Slc Transporters ◽  
Induced Pluripotent

Background: Multiple pharmacogenomic studies have identified the synonymous genomic variant rs7853758 (G>A, L461L) and the intronic variant rs885004 in SLC28A3 as statistically associated with a lower incidence of anthracycline-induced cardiotoxicity (AIC). However, the true causal variant(s), the cardioprotective mechanism of this locus, the role of SLC28A3 and other solute carrier (SLC) transporters in AIC, and the suitability of SLC transporters as targets for cardioprotective drugs has not been investigated. Methods: Six well-phenotyped, doxorubicin-treated pediatric patients from the original association study cohort were re-recruited and human induced pluripotent stem cell-derived cardiomyocytes were generated. Patient-specific doxorubicin-induced cardiotoxicity (DIC) was then characterized using assays of cell viability, activated caspase 3/7, and doxorubicin uptake. The role of SLC28A3 in DIC was then queried using overexpression and knockout of SLC28A3 in isogenic hiPSCs using a CRISPR/Cas9. Fine−mapping of the SLC28A3 locus was then completed after SLC28A3 resequencing and an extended in silico haplotype and functional analysis. Genome editing of potential causal variant was done using cytosine base editor. SLC28A3−AS1 overexpression was done using a lentiviral plasmid-based transduction and was validated using stranded RNA-Seq after ribosomal RNA depletion. Drug screening was done using the Prestwick drug library ( n = 1200) followed by in vivo validation in mice. The effect of desipramine on DOX cytotoxicity was also investigated in eight cancer cell lines. Results: Here, using the most commonly used anthracycline, doxorubicin, we demonstrate that patient-derived cardiomyocytes recapitulate the cardioprotective effect of the SLC28A3 locus and that SLC28A3 expression influences the severity of DIC. Using Nanopore¬-based fine-mapping and base editing we identify a novel cardioprotective SNP rs11140490 in the SLC28A3 locus which exerts its effect by regulating an antisense long noncoding-RNA ( SLC28A3-AS1 ) that overlaps with SLC28A3 . Using high-throughput drug screening in patient-derived cardiomyocytes and whole organism validation in mice, we identify the SLC competitive inhibitor desipramine as protective against DIC. Conclusions: This work demonstrates the power of the human induced pluripotent stem cell model to take a SNP from a statistical association through to drug discovery, providing human cell-tested data for clinical trials to attenuate DIC.

scholarly journals NKX3-1 is required for induced pluripotent stem cell reprogramming and can replace OCT4 in mouse and human iPSC induction

2018 ◽  
Vol 20 (8) ◽  
pp. 900-908 ◽  
Author(s):  
Thach Mai ◽  
Glenn J. Markov ◽  
Jennifer J. Brady ◽  
Adelaida Palla ◽  
Hong Zeng ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cell Reprogramming ◽  
Induced Pluripotent ◽  
Human Ipsc
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