Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells

Shinde, Vaibhav; Srinivasan, Sureshkumar Perumal; Henry, Margit; Rotshteyn, Tamara; Hescheler, Jürgen; Rahnenführer, Jörg; Grinberg, Marianna; Meisig, Johannes; Blüthgen, Nils; Waldmann, Tanja; Leist, Marcel; Hengstler, Jan G.; Sachinidis, Agapios

doi:10.1186/s13287-016-0449-2

Cited by 35 publications

(28 citation statements)

References 34 publications

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“…For example, when glucose metabolism is less efficient in hypoxic culture, cells may use glutamine for energy. Previous studies have demonstrated that, under normoxic conditions, glutamine is not used as an energy source by MSCs for cell growth; however, there is more glutamine consumption by MSCs in hypoxic culture than in normoxic culture …”

Section: Current Strategies Used To Construct the Bone Marrow Niche Imentioning

confidence: 99%

Strategies to retain properties of bone marrow–derived mesenchymal stem cellsex vivo

Yun

Tsai

2017

Annals of the New York Academy of Sciences

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Mesenchymal stem cells (MSCs) have been extensively used for cell therapies and tissue engineering. The current MSC strategy requires a large quantity of cells for such applications, which can be achieved through cell expansion in culture. In the body, stem cell fate is largely determined by their microenvironment, known as the niche. The complex and dynamic stem cell niche provides physical, mechanical, and chemical cues to collaboratively regulate cell activities. It remains a great challenge to maintain the properties of MSCs in culture. Constructing a microenvironment as an engineered stem cell niche in culture to maintain MSC phenotypes, properties, and functions is a viable strategy to address the issue. Here, we review the current understanding of MSC behavior in the bone marrow niche, describe different strategies to engineer an in vitro microenvironment for maintaining MSC properties and functions, and discuss previous findings on environmental factors critical to the modulation of MSC activities in engineered microenvironments.

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Section: Current Strategies Used To Construct the Bone Marrow Niche Imentioning

confidence: 99%

Strategies to retain properties of bone marrow–derived mesenchymal stem cellsex vivo

Yun

Tsai

2017

Annals of the New York Academy of Sciences

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“…HiPSC can easily be derived from individuals of different gender and ages, and have recently been used for several toxicological studies and shown to predict for example cardiac toxicity of cosmetic compounds (Chaudhari et al 2018;Luz and Tokar 2018). Their use for predicting developmental toxicity has also been validated, as transcriptome changes during multi-lineage differentiation upon exposure to valproic acid were similar between hESCs and hiPSCs (Shinde et al 2016).…”

Section: Introductionmentioning

confidence: 99%

A novel human pluripotent stem cell-based assay to predict developmental toxicity

et al. 2020

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There is a great need for novel in vitro methods to predict human developmental toxicity to comply with the 3R principles and to improve human safety. Human-induced pluripotent stem cells (hiPSC) are ideal for the development of such methods, because they are easy to retrieve by conversion of adult somatic cells and can differentiate into most cell types of the body. Advanced three-dimensional (3D) cultures of these cells, so-called embryoid bodies (EBs), moreover mimic the early developing embryo. We took advantage of this to develop a novel human toxicity assay to predict chemically induced developmental toxicity, which we termed the PluriBeat assay. We employed three different hiPSC lines from male and female donors and a robust microtiter plate-based method to produce EBs. We differentiated the cells into cardiomyocytes and introduced a scoring system for a quantitative readout of the assay—cardiomyocyte contractions in the EBs observed on day 7. Finally, we tested the three compounds thalidomide (2.3–36 µM), valproic acid (25–300 µM), and epoxiconazole (1.3–20 µM) on beating and size of the EBs. We were able to detect the human-specific teratogenicity of thalidomide and found the rodent toxicant epoxiconazole as more potent than thalidomide in our assay. We conclude that the PluriBeat assay is a novel method for predicting chemicals’ adverse effects on embryonic development.

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“…This initiative further developed the description of a tiered screening strategy and also exemplified the documentation of test compounds (Zimmer et al 2014). Assays resulting from the project demonstrated how omics technologies may be used in a quantitative way for toxicological prediction models (Pallocca et al 2016;Rempel et al 2015;Shinde et al 2015Shinde et al , 2016Shinde et al , 2017Waldmann et al 2017).…”

Section: Introductionmentioning

confidence: 99%

The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods

et al. 2020

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Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes. The EU-ToxRisk project developed a strategy to provide regulatorily valid data, and exemplified this using a panel of > 20 assays (with > 50 individual endpoints), each exposed to 19 well-known test compounds (e.g. rotenone, colchicine, mercury, paracetamol, rifampicine, paraquat, taxol). Examples of strategy implementation are provided for all aspects required to ensure data validity: (i) documentation of test methods in a publicly accessible database; (ii) deposition of standard operating procedures (SOP) at the European Union DB-ALM repository; (iii) test readiness scoring accoding to defined criteria; (iv) disclosure of the pipeline for data processing; (v) link of uncertainty measures and metadata to the data; (vi) definition of test chemicals, their handling and their behavior in test media; (vii) specification of the test purpose and overall evaluation plans. Moreover, data generation was exemplified by providing results from 25 reporter assays. A complete evaluation of the entire test battery will be described elsewhere. A major learning from the retrospective analysis of this large testing project was the need for thorough definitions of the above strategy aspects, ideally in form of a study pre-registration, to allow adequate interpretation of the data and to ensure overall scientific/toxicological validity.

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Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells

Cited by 35 publications

References 34 publications

Strategies to retain properties of bone marrow–derived mesenchymal stem cellsex vivo

Strategies to retain properties of bone marrow–derived mesenchymal stem cellsex vivo

A novel human pluripotent stem cell-based assay to predict developmental toxicity

The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods

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