Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity

A. Apáti, Nóra Varga, Tünde Berecz, Zsuzsa Erdei, L. Homolya, B. Sarkadi

???family-name???: Review article

Abstract

Introduction: Human pluripotent stem cells (hPSCs) are capable of differentiating into all types of cells in the body and so provide suitable toxicology screening systems even for hard-to-obtain human tissues. Since hPSCs can also be generated from differentiated cells and current gene editing technologies allow targeted genome modifications, hPSCs can be applied for drug toxicity screening both in normal and disease-specific models. Targeted hPSC differentiation is still a challenge but cardiac, neuronal or liver cells, and complex cellular models are already available for practical applications. Areas covered: The authors review new gene-editing and cell-biology technologies to generate sensitive toxicity screening systems based on hPSCs. Then the authors present the use of undifferentiated hPSCs for examining embryonic toxicity and discuss drug screening possibilities in hPSC-derived models. The authors focus on the application of human cardiomyocytes, hepatocytes, and neural cultures in toxicity testing, and discuss the recent possibilities for drug screening in a ‘body-on-a-chip’ model system. Expert opinion: hPSCs and their genetically engineered derivatives provide new possibilities to investigate drug toxicity in human tissues. The key issues in this regard are still the selection and generation of proper model systems, and the interpretation of the results in understanding in vivo drug effects.

???language???English
???pages???61-75
???numberOfPages???15
???journalAssociation???Expert Opinion on Drug Metabolism and Toxicology
???volume???15
???journalNumber???1
???DOIs???
???publicationStatus???Published - jan. 2 2019

Fingerprint

Pluripotent Stem Cells
Stem cells
Drug-Related Side Effects and Adverse Reactions
Toxicity
Screening
Pharmaceutical Preparations
Preclinical Drug Evaluations
Genes
Cytology
Tissue
Technology
Liver
Expert Testimony
Human Genome
Cardiac Myocytes
Toxicology
Cell Biology
Cell Differentiation
Hepatocytes
Derivatives

Keywords

    ASJC Scopus subject areas

    • Toxicology
    • Pharmacology

    Cite this

    Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity. / Apáti, A.; Varga, Nóra; Berecz, Tünde; Erdei, Zsuzsa; Homolya, L.; Sarkadi, B.

    ???in???: Expert Opinion on Drug Metabolism and Toxicology, ???journal.volume??? 15, ???journalNumber??? 1, 02.01.2019, ???pages??? 61-75.

    ???family-name???: Review article

    Apáti, A. ; Varga, Nóra ; Berecz, Tünde ; Erdei, Zsuzsa ; Homolya, L. ; Sarkadi, B. / Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity. ???in???: Expert Opinion on Drug Metabolism and Toxicology. 2019 ; ???journal.volume??? 15, ???journalNumber??? 1. ???pages??? 61-75.
    @article{423f2443878d4fce82c564ec737b6b3d,
    title = "Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity",
    abstract = "Introduction: Human pluripotent stem cells (hPSCs) are capable of differentiating into all types of cells in the body and so provide suitable toxicology screening systems even for hard-to-obtain human tissues. Since hPSCs can also be generated from differentiated cells and current gene editing technologies allow targeted genome modifications, hPSCs can be applied for drug toxicity screening both in normal and disease-specific models. Targeted hPSC differentiation is still a challenge but cardiac, neuronal or liver cells, and complex cellular models are already available for practical applications. Areas covered: The authors review new gene-editing and cell-biology technologies to generate sensitive toxicity screening systems based on hPSCs. Then the authors present the use of undifferentiated hPSCs for examining embryonic toxicity and discuss drug screening possibilities in hPSC-derived models. The authors focus on the application of human cardiomyocytes, hepatocytes, and neural cultures in toxicity testing, and discuss the recent possibilities for drug screening in a ‘body-on-a-chip’ model system. Expert opinion: hPSCs and their genetically engineered derivatives provide new possibilities to investigate drug toxicity in human tissues. The key issues in this regard are still the selection and generation of proper model systems, and the interpretation of the results in understanding in vivo drug effects.",
    keywords = "body-on-a-chip, cardiomyocytes, directed hPSC differentiation, hepatocytes, Human pluripotent stem cells (hPSCs), model cells for toxicity screening, neural cell cultures, stem cell-derived cellular models",
    author = "A. Ap{\'a}ti and N{\'o}ra Varga and T{\"u}nde Berecz and Zsuzsa Erdei and L. Homolya and B. Sarkadi",
    year = "2019",
    month = "1",
    day = "2",
    doi = "10.1080/17425255.2019.1558207",
    language = "English",
    volume = "15",
    pages = "61--75",
    journal = "Expert Opinion on Drug Metabolism and Toxicology",
    issn = "1742-5255",
    publisher = "Informa Healthcare",
    number = "1",

    }

    TY - JOUR

    T1 - Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity

    AU - Apáti, A.

    AU - Varga, Nóra

    AU - Berecz, Tünde

    AU - Erdei, Zsuzsa

    AU - Homolya, L.

    AU - Sarkadi, B.

    PY - 2019/1/2

    Y1 - 2019/1/2

    N2 - Introduction: Human pluripotent stem cells (hPSCs) are capable of differentiating into all types of cells in the body and so provide suitable toxicology screening systems even for hard-to-obtain human tissues. Since hPSCs can also be generated from differentiated cells and current gene editing technologies allow targeted genome modifications, hPSCs can be applied for drug toxicity screening both in normal and disease-specific models. Targeted hPSC differentiation is still a challenge but cardiac, neuronal or liver cells, and complex cellular models are already available for practical applications. Areas covered: The authors review new gene-editing and cell-biology technologies to generate sensitive toxicity screening systems based on hPSCs. Then the authors present the use of undifferentiated hPSCs for examining embryonic toxicity and discuss drug screening possibilities in hPSC-derived models. The authors focus on the application of human cardiomyocytes, hepatocytes, and neural cultures in toxicity testing, and discuss the recent possibilities for drug screening in a ‘body-on-a-chip’ model system. Expert opinion: hPSCs and their genetically engineered derivatives provide new possibilities to investigate drug toxicity in human tissues. The key issues in this regard are still the selection and generation of proper model systems, and the interpretation of the results in understanding in vivo drug effects.

    AB - Introduction: Human pluripotent stem cells (hPSCs) are capable of differentiating into all types of cells in the body and so provide suitable toxicology screening systems even for hard-to-obtain human tissues. Since hPSCs can also be generated from differentiated cells and current gene editing technologies allow targeted genome modifications, hPSCs can be applied for drug toxicity screening both in normal and disease-specific models. Targeted hPSC differentiation is still a challenge but cardiac, neuronal or liver cells, and complex cellular models are already available for practical applications. Areas covered: The authors review new gene-editing and cell-biology technologies to generate sensitive toxicity screening systems based on hPSCs. Then the authors present the use of undifferentiated hPSCs for examining embryonic toxicity and discuss drug screening possibilities in hPSC-derived models. The authors focus on the application of human cardiomyocytes, hepatocytes, and neural cultures in toxicity testing, and discuss the recent possibilities for drug screening in a ‘body-on-a-chip’ model system. Expert opinion: hPSCs and their genetically engineered derivatives provide new possibilities to investigate drug toxicity in human tissues. The key issues in this regard are still the selection and generation of proper model systems, and the interpretation of the results in understanding in vivo drug effects.

    KW - body-on-a-chip

    KW - cardiomyocytes

    KW - directed hPSC differentiation

    KW - hepatocytes

    KW - Human pluripotent stem cells (hPSCs)

    KW - model cells for toxicity screening

    KW - neural cell cultures

    KW - stem cell-derived cellular models

    UR - http://www.scopus.com/inward/record.url?scp=85059060071&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85059060071&partnerID=8YFLogxK

    U2 - 10.1080/17425255.2019.1558207

    DO - 10.1080/17425255.2019.1558207

    M3 - Review article

    VL - 15

    SP - 61

    EP - 75

    JO - Expert Opinion on Drug Metabolism and Toxicology

    T2 - Expert Opinion on Drug Metabolism and Toxicology

    JF - Expert Opinion on Drug Metabolism and Toxicology

    SN - 1742-5255

    IS - 1

    ER -