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Stem Cell Reports. 2017 May 9;8(5):1340-1353. doi: 10.1016/j.stemcr.2017.03.009.

Differentiation-Defective Human Induced Pluripotent Stem Cells Reveal Strengths and Limitations of the Teratoma Assay and In Vitro Pluripotency Assays.

Author information

1
Department of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
2
Department of Molecular Epidemiology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
3
GenomeScan B.V., Plesmanlaan 1D, 2333 BZ Leiden, the Netherlands.
4
Central Laboratory Animal Facility, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands. Electronic address: d.c.f.salvatori@lumc.nl.
5
Department of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands. Electronic address: c.m.a.h.freund@lumc.nl.

Abstract

The ability to form teratomas in vivo containing multiple somatic cell types is regarded as functional evidence of pluripotency for human pluripotent stem cells (hPSCs). Since the Teratoma assay is animal dependent, laborious, and only qualitative, the PluriTest and the hPSC ScoreCard assay have been developed as in vitro alternatives. Here we compared normal hPSCs, induced hPSCs (hiPSCs) with reactivated reprogramming transgenes, and human embryonal carcinoma cells (hECs) in these assays. While normal hPSCs gave rise to typical teratomas, the xenografts of the hECs and the hiPSCs with reactivated reprogramming transgenes were largely undifferentiated and malignant. The hPSC ScoreCard assay confirmed the line-specific differentiation propensities in vitro. However, when undifferentiated cells were analyzed by the PluriTest, only hECs were identified as abnormal whereas all other cell lines were indistinguishable and resembled normal hPSCs. Our results indicate that pluripotency assays are best selected on the basis of intended downstream applications.

KEYWORDS:

PluriTest; TeratoScore; differentiation-defective; hPSC ScoreCard; human pluripotent stem cell; malignancy; pluripotency assay; teratoma; tumorigenicity

PMID:
28494940
PMCID:
PMC5425621
DOI:
10.1016/j.stemcr.2017.03.009
[Indexed for MEDLINE]
Free PMC Article

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