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

Thomas F. Allison, Peter W. Andrews*, Yishai Avior, Ivana Barbaric, Nissim Benvenisty, Christoph Bock, Jennifer Brehm, Oliver Brüstle, Ivan Damjanov, Andrew Elefanty, Daniel Felkner, Paul J. Gokhale, Florian Halbritter, Lyn E. Healy, Tim X. Hu, Barbara B. Knowles, Jeanne F. Loring, Tenneille E. Ludwig, Robyn Mayberry, Suzanne MicallefJameelah S. Mohamed, Franz Josef Müller, Christine L. Mummery, Norio Nakatsuji, Elizabeth S. Ng, Steve K.W. Oh, Orla O'Shea, Martin F. Pera, Benjamin Reubinoff, Paul Robson, Janet Rossant, Bernhard M. Schuldt, Davor Solter, Koula Sourris, Glyn Stacey, Edouard G. Stanley, Hirofumi Suemori, Kazutoshi Takahashi, Shinya Yamanaka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

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.

Original languageAmerican English
Article number1925
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

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© 2018 The Author(s).

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