Unknown,Transcriptomics,Genomics,Proteomics

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Study of the consistency, comparability and identity of different Dendritic cells productions for clinical use

ABSTRACT: Gene expression profiling of monocyte-derived Dendritic cells manufactured several times from one healthy donor and one single time from 8 different healthy donors to test the sources of variability Sources tested: Assay-related variability (8 samples), Manufacture-related variability (5 samples), Intra-donor-related variability (5 samples), inter-donor-related variability (9 samples) 4 different levels of variability were accounted: Assay, manufacture, intradonor, and interdonor

ORGANISM(S): Homo sapiens

SUBMITTER: Luciano Castiello

PROVIDER: E-GEOD-31195 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Many oncology drugs have been found to induce cardiotoxicity in a subset of patients, which significantly limits their clinical use and impedes the benefit of lifesaving anti-cancer treatments. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carry donor-specific genetic information and have been proposed for explore the inter-individual difference in oncology drug-induced cardiotoxicity. Herein, we evaluated the inter- and intra- individual variability of iPSC-CM-related assays and presented a practical approach for using donor-specific iPSC-CMs to predict personalized doxorubicin (DOX)-induced cardiotoxicity (DIC) prior to chemotherapy. Our findings demonstrated that donor-specific iPSC-CMs exhibited greater line-to-line variability than the intra-individual variability in impedance cytotoxicity and transcriptome assays. The variable and dose-dependent cytotoxic responses of iPSC-CMs resembled those observed in clinical practice, and largely replicated the reported mechanisms of DIC. By categorizing iPSC-CMs into DOX-resistant and DOX-sensitive cell lines based on their phenotypic reactions to DOX, we found that the sensitivity of donor-specific iPSC-CMs to DOX may predict in vivo DIC risk. Furthermore, we assessed the limitations of the model for identification of potential genetic/molecular biomarker and pinpointed a differentially expressed gene, DND microRNA-mediated repression inhibitor 1 (DND1), between the DOX-resistant and DOX-sensitive iPSC-CMs. We also discussed the selection of DOX dose and exposure duration for inter-individual variability of DIC assessment. Our results support the utility of donor-specific iPSC-CMs in assessing inter-individual difference and enabling personalized cardiotoxicity prediction. Further studies will encompass a large panel of donor-specific iPSC-CMs to investigate the role of the DND1 and known DIC genetic variants, and to identify potential novel molecular and genetic biomarkers for predicting DOX and other oncology drug-induced cardiotoxicity.

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Study of the consistency, comparability and identity of different Dendritic cells productions for clinical use

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