scholarly journals Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity

2020 ◽  
Vol 174 (2) ◽  
pp. 189-209 ◽  
Author(s):  
Todd J Zurlinden ◽  
Katerine S Saili ◽  
Nathaniel Rush ◽  
Parth Kothiya ◽  
Richard S Judson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Animal Studies ◽  
Developmental Toxicity ◽  
Embryonic Stem ◽  
High Specificity ◽  
Chemical Exposure ◽  
Toxicity Screening ◽  
In Silico Models

Abstract The Stemina devTOX quickPredict platform is a human pluripotent stem cell-based assay that predicts the developmental toxicity potential based on changes in cellular metabolism following chemical exposure [Palmer, J. A., Smith, A. M., Egnash, L. A., Conard, K. R., West, P. R., Burrier, R. E., Donley, E. L. R., and Kirchner, F. R. (2013). Establishment and assessment of a new human embryonic stem cell-based biomarker assay for developmental toxicity screening. Birth Defects Res. B Dev. Reprod. Toxicol. 98, 343–363]. Using this assay, we screened 1065 ToxCast phase I and II chemicals in single-concentration or concentration-response for the targeted biomarker (ratio of ornithine to cystine secreted or consumed from the media). The dataset from the Stemina (STM) assay is annotated in the ToxCast portfolio as STM. Major findings from the analysis of ToxCast_STM dataset include (1) 19% of 1065 chemicals yielded a prediction of developmental toxicity, (2) assay performance reached 79%–82% accuracy with high specificity (> 84%) but modest sensitivity (< 67%) when compared with in vivo animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain. The results of this study will be useful to improving our ability to predict in vivo developmental toxicants based on in vitro data and in silico models.

scholarly journals In vitro and in vivo analyses of human embryonic stem cell-derived dopamine neurons

2005 ◽  
Vol 92 (5) ◽  
pp. 1265-1276 ◽  
Author(s):  
Chang-Hwan Park ◽  
Yang-Ki Minn ◽  
Ji-Yeon Lee ◽  
Dong Ho Choi ◽  
Mi-Yoon Chang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Dopamine Neurons

scholarly journals Znanstvena istraživanja u 21. stoljeću - etički aspekti uporabe laboratorijskih životinja i alternativni modeli

2022 ◽  
Vol 53 (5) ◽  
Author(s):  
Ivana Kmetič ◽  
Monika Roller ◽  
Marina Miletić ◽  
Teuta Murati
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryo Culture ◽  
Embryonic Stem ◽  
Whole Embryo Culture ◽  
Cell Test

U toksikološkim istraživanjima uz uporabu klasičnih (in vivo) istraživanja, primjenjuju se alternativni test sustavi. Korištenje laboratorijskih životinja, embrija, humanog i animalnog tkiva, kultura stanica i fetalnog seruma u istraživanjima smatra se etički problematičnim te se ograničava zakonima, pravilnicima i praksom. Razmatranjem načina kojima bi se neetičnost mogla izbjeći, došlo je do razvoja “3R” načela (akronim za tri pristupa koja bi se trebala provoditi pri istraživanjima na laboratorijskim životinjama), a to su: smanjenje/racionalizacija uporabe laboratorijskih životinja (engl. Reduction), načelo njihove zamjene (engl. Replacement) i poboljšanje uvjeta uzgoja, smještaja i skrbi za životinje (engl. Refinement). Većina je alternativnih testova toksičnosti još uvijek u postupku validacije. Pojedini in vitro testovi za istraživanja embriotoksičnosti (etički posebno osjetljivo područje) koja su priznala nadležna regulatorna tijela, su EST (engl. Embryonic Stem cell Test), WEC (engl. Whole- Embryo Culture) i MM (engl. MicroMass) test. Standardizacija protokola i uvođenje novih in vitro modela predstavlja važan segment napretka u toksikološkim istraživanjima. Znanstvena budućnost tu vidi mogućnost razvoja i implementacije načela etičnosti u istraživanja primjenjujući sustave koji će promišljeno i bez korištenja živih organizama dijelom nadomjestiti metode u biomedicini, veterinarskoj medicini, biotehnologiji i užem smislu - toksikologiji i farmakologiji.

Accept or Reject: The Role of Immune Tolerance in the Development of Stem Cell Therapies and Possible Future Approaches

2020 ◽  
pp. 019262332091824
Author(s):  
Richard Haworth ◽  
Michaela Sharpe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Immune Recognition ◽  
Cell Of Origin ◽  
In Vivo Models ◽  
Cell Product ◽  
A Cell

In 2011, Goldring and colleagues published a review article describing the potential safety issues of novel stem cell-derived treatments. Immunogenicity and immunotoxicity of the administered cell product were considered risks in the light of clinical experience of transplantation. The relative immunogenicity of mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) was being addressed through in vitro and in vivo models. But the question arose as to whether the implanted cells needed to be identical to the recipient in every respect, including epigenetically, to evade immune recognition? If so, this set a high bar which may preclude use of many cells derived from iPSCs which have vestiges of a fetal phenotype and epigenetic memory of their cell of origin. However, for autologous iPSCs, the immunogenicity reduces once the surface antigen expression profile becomes close to that of the parent somatic cells. Therefore, a cell product containing incompletely differentiated cells could be more immunogenic. The properties of the administered cells, the immune privilege of the administration site, and the host immune status influence graft success or failure. In addition, the various approaches available to characterize potential immunogenicity of a cell therapy will be discussed.

Global transcriptional profiling reveals similarities and differences between human stem cell-derived cardiomyocyte clusters and heart tissue

2012 ◽  
Vol 44 (4) ◽  
pp. 245-258 ◽  
Author(s):  
Jane Synnergren ◽  
Caroline Améen ◽  
Andreas Jansson ◽  
Peter Sartipy
Keyword(s):  
Stem Cell ◽  
Ion Channels ◽  
Human Heart ◽  
Embryonic Stem ◽  
Heart Tissue ◽  
Phenotypic Characterization ◽  
Adult Heart ◽  
Promising Source

It is now well documented that human embryonic stem cells (hESCs) can differentiate into functional cardiomyocytes. These cells constitute a promising source of material for use in drug development, toxicity testing, and regenerative medicine. To assess their utility as replacement or complement to existing models, extensive phenotypic characterization of the cells is required. In the present study, we used microarrays and analyzed the global transcription of hESC-derived cardiomyocyte clusters (CMCs) and determined similarities as well as differences compared with reference samples from fetal and adult heart tissue. In addition, we performed a focused analysis of the expression of cardiac ion channels and genes involved in the Ca2+-handling machinery, which in previous studies have been shown to be immature in stem cell-derived cardiomyocytes. Our results show that hESC-derived CMCs, on a global level, have a highly similar gene expression profile compared with human heart tissue, and their transcriptional phenotype was more similar to fetal than to adult heart. Despite the high similarity to heart tissue, a number of significantly differentially expressed genes were identified, providing some clues toward understanding the molecular difference between in vivo sourced tissue and stem cell derivatives generated in vitro. Interestingly, some of the cardiac-related ion channels and Ca2+-handling genes showed differential expression between the CMCs and heart tissues. These genes may represent candidates for future genetic engineering to create hESC-derived CMCs that better mimic the phenotype of the cardiomyocytes present in the adult human heart.

scholarly journals Relative Developmental Toxicity of Glycol Ether Alkoxy Acid Metabolites in the Embryonic Stem Cell Test as compared with the In Vivo Potency of their Parent Compounds

2009 ◽  
Vol 110 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Esther de Jong ◽  
Jochem Louisse ◽  
Miriam Verwei ◽  
Bas J. Blaauboer ◽  
Johannes J. M. van de Sandt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Developmental Toxicity ◽  
Embryonic Stem ◽  
Glycol Ether ◽  
Cell Test ◽  
Acid Metabolites

Relative developmental toxicity of glycol ethers in the embryonic stem cell test and comparison to their in vivo potency ranking

2009 ◽  
Vol 28 (2) ◽  
pp. 133
Author(s):  
Esther de Jong ◽  
Jochem Louisse ◽  
Miriam Verwei ◽  
Bas J. Blaauboer ◽  
Han van de Sandt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Developmental Toxicity ◽  
Embryonic Stem ◽  
Glycol Ethers ◽  
Cell Test ◽  
Potency Ranking
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