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

Stem Cell Reports
Marga J BoumaChristian Freund

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.

Citations

Aug 1, 2018·Expert Opinion on Biological Therapy·Tilman ZieglerChristian Kupatt
Sep 13, 2018·Regenerative Medicine·Stephen SullivanJihwan Song
Feb 15, 2018·Scientific Reports·Vardine SahakyanMaurilio Sampaolesi
Jun 1, 2018·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Ryunosuke UmeharaMasahiko Kuroda
Jul 3, 2019·Stem Cells and Development·Kyle BurrellIna Dobrinski
Aug 10, 2019·World Journal of Stem Cells·Li-Ping Liu, Yun-Wen Zheng
Aug 14, 2020·ILAR Journal·Steven M Niemi
May 6, 2020·BioResearch Open Access·Akram Al AbbarSyahril Abdullah
Sep 22, 2020·Current Protocols in Stem Cell Biology·Marga J BoumaChristian Freund

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Methods Mentioned

BETA
transgenic
FCS
fluorescence-activated cell sorting
xenografts
xenograft
FACS

Software Mentioned

ScoreCard
Stemdiff
TeratoScore
hPSC ScoreCard
PluriTest
GenomeScan

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