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.

Details

Title
Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells
Author
Allison, Thomas F 1 ; Andrews, Peter W 2   VIAFID ORCID Logo  ; Avior, Yishai 3 ; Barbaric, Ivana 2 ; Benvenisty, Nissim 3 ; Bock, Christoph 4   VIAFID ORCID Logo  ; Brehm, Jennifer 5 ; Brüstle, Oliver 6 ; Damjanov, Ivan 7   VIAFID ORCID Logo  ; Elefanty, Andrew 8 ; Felkner, Daniel 5 ; Gokhale, Paul J 2 ; Halbritter, Florian 9   VIAFID ORCID Logo  ; Healy, Lyn E 10 ; Hu, Tim X 11   VIAFID ORCID Logo  ; Knowles, Barbara B 12 ; Loring, Jeanne F 13   VIAFID ORCID Logo  ; Ludwig, Tenneille E 5 ; Mayberry, Robyn 8 ; Micallef, Suzanne 8 ; Mohamed, Jameelah S 11 ; Müller, Franz-Josef 14   VIAFID ORCID Logo  ; Mummery, Christine L 15 ; Nakatsuji, Norio 16 ; Ng, Elizabeth S 8 ; Oh, Steve K W 17 ; Orla O’Shea 18 ; Pera, Martin F 19 ; Reubinoff, Benjamin 20 ; Robson, Paul 21   VIAFID ORCID Logo  ; Rossant, Janet 22   VIAFID ORCID Logo  ; Schuldt, Bernhard M 23 ; Solter, Davor 24 ; Sourris, Koula 8 ; Stacey, Glyn 25 ; Stanley, Edouard G 8 ; Suemori, Hirofumi 26 ; Takahashi, Kazutoshi 27 ; Yamanaka, Shinya 28 

 Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, UK; UCLA School of Medicine, Department of Biological Chemistry, Los Angeles, CA, USA 
 Centre for Stem Cell Biology, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, UK 
 The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel 
 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria; Max Planck Institute for Informatics, Saarland Informatics Campus, Saarbrücken, Germany 
 WiCell Research Institute Inc., Madison, WI, USA 
 Institute of Reconstructive Neurobiology, LIFE and BRAIN Center, University of Bonn Medical Faculty, Bonn, Germany 
 Department of Pathology, The University of Kansas School of Medicine, Kansas City, KS, USA 
 Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia 
 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria 
10  UK Stem Cell Bank, Advanced Therapies Division, NIBSC-MHRA, Blanche Ln, South Mimms, Potters Bar, UK; The Francis Crick Institute, London, UK 
11  Genome Institute of Singapore, Singapore, Singapore 
12  Jackson Laboratory, Bar Harbor, ME, USA; Siriraj Center of Excellence in Stem Cell Research, Mahidol University, Bangkok, Thailand 
13  The Scripps Research Institute, La Jolla, CA, USA 
14  Department of Genome Regulation, Max-Planck-Institute for Molecular Genetics, Berlin, Germany; Zentrum für Integrative Psychiatrie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany 
15  Leiden University Medical Center, Leiden, The Netherlands 
16  Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan 
17  Bioprocessing Technology Institute, Singapore, Singapore 
18  UK Stem Cell Bank, Advanced Therapies Division, NIBSC-MHRA, Blanche Ln, South Mimms, Potters Bar, UK 
19  Stem Cells Australia, The University of Melbourne, Parkville, VIC, Australia; Department of Anatomy and Neurosciences, The University of Melbourne, Parkville, VIC, Australia; Florey Neuroscience and Mental Health Institute, Parkville, VIC, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; The Jackson Laboratory, Bar Harbor, ME, USA 
20  Department of Obstetrics and Gynecology, and the Hadassah Human Embryonic Stem Cells Research Center, The Goldyne-Savad Institute of Gene Therapy, Hadassah-Hebrew University Hospital, Jerusalem, Israel 
21  Genome Institute of Singapore, Singapore, Singapore; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, USA 
22  Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada 
23  Zentrum für Integrative Psychiatrie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany 
24  Siriraj Center of Excellence in Stem Cell Research, Mahidol University, Bangkok, Thailand; Max Planck Society, Munich, Germany 
25  UK Stem Cell Bank, Advanced Therapies Division, NIBSC-MHRA, Blanche Ln, South Mimms, Potters Bar, UK; The International Stem Cell Banking Initiative, Barley, Herts, UK 
26  Laboratory of Embryonic Stem Cell research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan 
27  Center for iPS cell Research and Application, Kyoto University, Kyoto, Japan 
28  Center for iPS cell Research and Application, Kyoto University, Kyoto, Japan; Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA 
Pages
1-15
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2039260630
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.