Identification of Unsafe Human Induced Pluripotent Stem Cell Lines Using a Robust Surrogate Assay for Pluripotency

Polanco, Juan Carlos, Ho, Mirabelle S. H., Wang, Bei, Zhou, Qi, Wolvetang, Ernst, Mason, Elizabeth, Wells, Christine A., Kolle, Gabriel, Grimmond, Sean M., Bertoncello, Ivan, O'Brien, Carmel and Laslett, Andrew L. (2013) Identification of Unsafe Human Induced Pluripotent Stem Cell Lines Using a Robust Surrogate Assay for Pluripotency. Stem Cells, 31 8: 1498-1510. doi:10.1002/stem.1425

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Author Polanco, Juan Carlos
Ho, Mirabelle S. H.
Wang, Bei
Zhou, Qi
Wolvetang, Ernst
Mason, Elizabeth
Wells, Christine A.
Kolle, Gabriel
Grimmond, Sean M.
Bertoncello, Ivan
O'Brien, Carmel
Laslett, Andrew L.
Title Identification of Unsafe Human Induced Pluripotent Stem Cell Lines Using a Robust Surrogate Assay for Pluripotency
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
Publication date 2013-08-01
Year available 2013
Sub-type Article (original research)
DOI 10.1002/stem.1425
Open Access Status DOI
Volume 31
Issue 8
Start page 1498
End page 1510
Total pages 13
Place of publication Durham, United States
Publisher AlphaMed Press
Language eng
Abstract Human induced pluripotent stem cells (hiPSC) have the potential to generate healthy cells and tissues for the study and medical treatment of a large number of diseases. The utility of putative hiPSC-based therapies is constrained by a lack of robust quality-control assays that address the stability of the cells or their capacity to form teratomas after differentiation. Here we report that virally derived hiPSC, but not human embryonic stem cells (hESC) or hiPSC derived using episomal nonintegrating vectors, exhibit a propensity to revert to a pluripotent phenotype following differentiation. This instability was revealed using our published method to identify pluripotent cells undergoing very early-stage differentiation in standard hESC cultures, by fluorescence activated cell sorting (FACS) based on expression of the cell surface markers TG30 (CD9) and GCTM-2. Differentiated cells cultured post-FACS fractionation from virally derived hiPSC lines reacquired immunoreactivity to TG30 (CD9) and GCTM-2, formed stem cell-like colonies, and re-expressed canonical pluripotency markers. Furthermore, differentiated cells from pluripotency-reverting hiPSC lines generated teratomas in immunocompromised mice, raising concerns about their safety in downstream applications. In contrast, differentiated cell populations from hESC and episomally derived hiPSC did not show any of these abnormalities. Our assays may be used to identify “unsafe” hiPSC cell lines and this information should be considered when selecting hiPSC lines for clinical use and indicate that experiments using these “unsafe” hiPSC lines should be interpreted carefully.
Keyword Induced pluripotent stem cells
Pluripotent stem cells
Embryonic stem cells
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID P01 HL094374
DP2 DK102258
U01 HL100405
U01 HL100395
U01 HL099997
T32 HL007312
T32 EB001650
R01 HL084642
P01 GM081619
Institutional Status UQ

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