StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells

Yamane, Junko; Wada, Tatsuo; Otsuki, Hironori; Inomata, Koji; Suzuki, Mutsumi; Hisaki, Tomoka; Sekine, Satoshi; Kouzuki, Hirokazu; Kobayashi, Kensuke; Sone, Hirohito; Yamashita, Jun; Osawa, Mitsujiro; Saito, Megumu K.; Fujibuchi, Wataru

doi:10.1016/j.isci.2022.104538

Cited by 3 publications

(1 citation statement)

References 75 publications

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“…These differentiated cells can use in various studies, such as risk assessment, drug effects evaluation, and disease mechanisms elucidation. In human studies, pluripotent stem cells already use for various studies, such as the evaluation of drugs, pollutant risk, and risk assessment of infectious diseases [ 2 – 5 ]. In contrast, the application of iPSC technology to avian species is scarce.…”

Section: Introductionmentioning

confidence: 99%

Organoids containing neural-like cells derived from chicken iPSCs respond to poly:IC through the RLR family

et al. 2023

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There is still much room for development in pluripotent stem cell research on avian species compared to human stem cell studies. Neural cells are useful for the evaluation of risk assessment of infectious diseases since several avian species die of encephalitis derived from infectious diseases. In this study, we attempted to develop induced pluripotent stem cells (iPSCs) technology for avian species by forming organoids containing neural-like cells. In our previous study, we established two types iPSCs from chicken somatic cells, the first is iPSCs with PB-R6F reprogramming vector and the second is iPSCs with PB-TAD-7F reprogramming vector. In this study, we first compared the nature of these two cell types using RNA-seq analysis. The total gene expression of iPSCs with PB-TAD-7F was closer to that of chicken ESCs than that of iPSCs with PB-R6F; therefore, we used iPSCs with PB-TAD-7F to form organoids containing neural-like cells. We successfully established organoids containing neural-like cells from iPSCs using PB-TAD-7F. Furthermore, our organoids responded to poly:IC through the RIG-I-like receptor (RLR) family. In this study, we developed iPSCs technology for avian species via organoid formation. In the future, organoids containing neural-like cells from avian iPSCs can develop as a new evaluation tool for infectious disease risk in avian species, including endangered avian species.

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Section: Introductionmentioning

confidence: 99%

Organoids containing neural-like cells derived from chicken iPSCs respond to poly:IC through the RLR family

et al. 2023

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CRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency

Goolab,

Terburgh,

du Plessis

et al. 2025

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Mixup SVM Learning for Compound Toxicity Prediction Using Human Pluripotent Stem Cells

MOCHIDA,

NAKAJIMA,

ONO

et al. 2024

IEICE Trans. Inf. & Syst.

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Drug discovery, characterized by its time-consuming and costly nature, demands approximately 9 to 17 years and around two billion dollars for development. Despite the extensive investment, about 90% of drugs entering clinical trials face withdrawal, with compound toxicity accounting for 30% of these instances. Ethical concerns and the discrepancy in mechanisms between humans and animals have prompted regulatory restrictions on traditional animal-based toxicity prediction methods. In response, human pluripotent stem cell-based approaches have emerged as an alternative. This paper investigates the scalability challenges inherent in utilizing pluripotent stem cells due to the costly nature of RNAseq and the lack of standardized protocols. To address these challenges, we propose applying Mixup data augmentation, a successful technique in deep learning, to kernel SVM, facilitated by Stochastic Dual Coordinate Ascent (SDCA). Our novel approach, Exact SDCA, leverages intermediate class labels generated through Mixup, offering advancements in both efficiency and effectiveness over conventional methods. Numerical experiments reveal that Exact SDCA outperforms Approximate SDCA and SGD in attaining optimal solutions with significantly fewer epochs. Real data experiments further demonstrate the efficacy of multiplexing gene networks and applying Mixup in toxicity prediction using pluripotent stem cells.

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StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells

Cited by 3 publications

References 75 publications

Organoids containing neural-like cells derived from chicken iPSCs respond to poly:IC through the RLR family

Organoids containing neural-like cells derived from chicken iPSCs respond to poly:IC through the RLR family

CRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency

Mixup SVM Learning for Compound Toxicity Prediction Using Human Pluripotent Stem Cells

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