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 Micallef; Jameelah 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

doi:10.1038/s41467-018-04011-3

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

Department of Genetics

Research output: Contribution to journal › Article › peer-review

85 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 language	English
Article number	1925
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04011-3
State	Published - 1 Dec 2018

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Publisher Copyright:
© 2018 The Author(s).

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Allison, T. F., Andrews, P. W., Avior, Y., Barbaric, I., Benvenisty, N., Bock, C., Brehm, J., Brüstle, O., Damjanov, I., Elefanty, A., Felkner, D., Gokhale, P. J., Halbritter, F., Healy, L. E., Hu, T. X., Knowles, B. B., Loring, J. F., Ludwig, T. E., Mayberry, R., ... Yamanaka, S. (2018). Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells. Nature Communications, 9(1), Article 1925. https://doi.org/10.1038/s41467-018-04011-3

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title = "Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells",

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.",

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

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Allison, TF, Andrews, PW, Avior, Y, Barbaric, I, Benvenisty, N, Bock, C, Brehm, J, Brüstle, O, Damjanov, I, Elefanty, A, Felkner, D, Gokhale, PJ, Halbritter, F, Healy, LE, Hu, TX, Knowles, BB, Loring, JF, Ludwig, TE, Mayberry, R, Micallef, S, Mohamed, JS, Müller, FJ, Mummery, CL, Nakatsuji, N, Ng, ES, Oh, SKW, O'Shea, O, Pera, MF, Reubinoff, B, Robson, P, Rossant, J, Schuldt, BM, Solter, D, Sourris, K, Stacey, G, Stanley, EG, Suemori, H, Takahashi, K & Yamanaka, S 2018, 'Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells', Nature Communications, vol. 9, no. 1, 1925. https://doi.org/10.1038/s41467-018-04011-3

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AU - Allison, Thomas F.

AU - Andrews, Peter W.

AU - Avior, Yishai

AU - Barbaric, Ivana

AU - Benvenisty, Nissim

AU - Bock, Christoph

AU - Brehm, Jennifer

AU - Brüstle, Oliver

AU - Damjanov, Ivan

AU - Elefanty, Andrew

AU - Felkner, Daniel

AU - Gokhale, Paul J.

AU - Halbritter, Florian

AU - Healy, Lyn E.

AU - Hu, Tim X.

AU - Knowles, Barbara B.

AU - Loring, Jeanne F.

AU - Ludwig, Tenneille E.

AU - Mayberry, Robyn

AU - Micallef, Suzanne

AU - Mohamed, Jameelah S.

AU - Müller, Franz Josef

AU - Mummery, Christine L.

AU - Nakatsuji, Norio

AU - Ng, Elizabeth S.

AU - Oh, Steve K.W.

AU - O'Shea, Orla

AU - Pera, Martin F.

AU - Reubinoff, Benjamin

AU - Robson, Paul

AU - Rossant, Janet

AU - Schuldt, Bernhard M.

AU - Solter, Davor

AU - Sourris, Koula

AU - Stacey, Glyn

AU - Stanley, Edouard G.

AU - Suemori, Hirofumi

AU - Takahashi, Kazutoshi

AU - Yamanaka, Shinya

PY - 2018/12/1

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

Abstract

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