4.8 Article

Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells

Journal

NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04011-3

Keywords

-

Funding

  1. International Stem Cell Forum [MC_qA137863]
  2. Australian Stem Cell Centre, Stem Cells Australia
  3. Juvenile Diabetes Research Foundation
  4. National Health and Medical Research Council (NHMRC) of Australia
  5. New Frontiers Group award of the Austrian Academy of Sciences
  6. ERC Starting Grant (European Union's Horizon research and innovation programme) [679146]
  7. German Research Council (DFG) [HA 7723/1-1]
  8. BMBF [13GW0128A, 01GM1513D]
  9. Deutsche Forschungsgemeinschaft: German Research Foundation
  10. DFG [MU 3231/3-1]
  11. DFG within the framework of the Schleswig-Holstein Cluster of Excellence, EXC 306 Inflammation at Interfaces
  12. California Institute for Regenerative Medicine grant [RT3-0765, GCIR-06673-A, DISC2-09073]
  13. NIH [R01 NS09204202]
  14. Phase IV UK Stem Cell Bank grant from the Medical Research Council
  15. Biotechnology and Biological Sciences Research Council [MR/L01324X/1]
  16. Australian Research Council [SRI10001002]
  17. German Federal Ministry of Education and Research [01EK1603A, 01ZX1314A]
  18. European Union's Horizon Research and Innovation Programme [667301]
  19. European Community's Seventh Framework Programme (FP7) [602423]
  20. Horizon Research and Innovation Programme [668724]
  21. UK Regenerative Medicine, MRC Reference [MR/L012537/1]
  22. Medical Research Council, MRC Reference [MR/N009371/1]
  23. Rosetrees Trust
  24. Azrieli Foundation
  25. H2020 Societal Challenges Programme [667301] Funding Source: H2020 Societal Challenges Programme
  26. MRC [MR/L012537/1, MR/L012650/1, MR/N009371/1, MC_qA137916] Funding Source: UKRI

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The International Stem Cell Initiative compared several commonly used approaches to assess human pluripotent stem cells (PSC). PluriTest predicts pluripotency through bioinformatic analysis of the transcriptomes of undifferentiated cells, whereas, embryoid body (EB) formation in vitro and teratoma formation in vivo provide direct tests of differentiation. Here we report that EB assays, analyzed after differentiation under neutral conditions and under conditions promoting differentiation to ectoderm, mesoderm, or endoderm lineages, are sufficient to assess the differentiation potential of PSCs. However, teratoma analysis by histologic examination and by TeratoScore, which estimates differential gene expression in each tumor, not only measures differentiation but also allows insight into a PSC's malignant potential. Each of the assays can be used to predict pluripotent differentiation potential but, at this stage of assay development, only the teratoma assay provides an assessment of pluripotency and malignant potential, which are both relevant to the pre-clinical safety assessment of PSCs.

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