High-Content Assay Multiplexing for Toxicity Screening in Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Hepatocytes

Grimm, Fabian A.; Iwata, Yasuhiro; Sirenko, Oksana; Bittner, Michael; Rusyn, Ivan

doi:10.1089/adt.2015.659

ASSAY and Drug Development Technologies

2015

DOI: 10.1089/adt.2015.659

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High-Content Assay Multiplexing for Toxicity Screening in Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Hepatocytes

Fabian A. Grimm

¹

,

Yasuhiro Iwata

²

,

Oksana Sirenko

³

et al.

Abstract: Cell-based high-content screening (HCS) assays have become an increasingly attractive alternative to traditional in vitro and in vivo testing in pharmaceutical drug development and toxicological safety assessment. The time- and cost-effectiveness of HCS assays, combined with the organotypic nature of human induced pluripotent stem cell (iPSC)-derived cells, open new opportunities to employ physiologically relevant in vitro model systems to improve screening for potential chemical hazards. In this study, we use… Show more

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Cited by 219 publications

(143 citation statements)

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“…Our second key finding was that the degree of inter-individual variability in responses to treatment depends reproducibly on chemical and phenotypic endpoints. In cardiomyocytes derived from the standard commercial iCell cardiomyocyte product offered by Cellular Dynamics International (individual 1434), the results for our selected reference compounds are in excellent agreement with previous reports (Grimm et al, 2015;Sirenko et al, 2013aSirenko et al, ,b, 2017. Population-level differences in drug response are evident and the degree of interindividual variability in responses differ depending on chemical and endpoint.…”

Section: Discussionsupporting

confidence: 91%

A human population-based organotypic in vitro model for cardiotoxicity screening

Grimm¹

2018

ALTEX

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Our second key finding was that the degree of inter-individual variability in responses to treatment depends reproducibly on chemical and phenotypic endpoints. In cardiomyocytes derived from the standard commercial iCell cardiomyocyte product offered by Cellular Dynamics International (individual 1434), the results for our selected reference compounds are in excellent agreement with previous reports (Grimm et al, 2015;Sirenko et al, 2013aSirenko et al, ,b, 2017. Population-level differences in drug response are evident and the degree of interindividual variability in responses differ depending on chemical and endpoint.…”

Section: Discussionsupporting

confidence: 91%

A human population-based organotypic in vitro model for cardiotoxicity screening

Grimm¹

2018

ALTEX

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Our second key finding was that the degree of inter-individual variability in responses to treatment depends reproducibly on chemical and phenotypic endpoints. In cardiomyocytes derived from the standard commercial iCell cardiomyocyte product offered by Cellular Dynamics International (individual 1434), the results for our selected reference compounds are in excellent agreement with previous reports (Grimm et al, 2015;Sirenko et al, 2013aSirenko et al, ,b, 2017. Population-level differences in drug response are evident and the degree of inter-individual variability in responses differs depending on chemical and endpoint.…”

Section: Discussionsupporting

confidence: 91%

A human population-based organotypic in vitro model for cardiotoxicity screening_suppl

Grimm

¹

2018

ALTEX

0

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…In cardiomyocytes derived from the standard commercial iCell cardiomyocyte product offered by Cellular Dynamics International (individual 1434), the results for our selected reference compounds are in excellent agreement with previous reports (Grimm et al, 2015; Sirenko et al, 2013a,b, 2017). Population-level differences in drug response are evident and the degree of inter-individual variability in responses differ depending on chemical and endpoint.…”

Section: Discussionsupporting

confidence: 90%

A human population-based organotypic in vitro model for cardiotoxicity screening

Grimm

¹

2018

ALTEX

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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